The high morbidity and mortality rate of individuals with human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)coinfected with Mycobacterium tuberculosis(MTB)is a tough challenge for current globa...The high morbidity and mortality rate of individuals with human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)coinfected with Mycobacterium tuberculosis(MTB)is a tough challenge for current global tuberculosis prevention and control efforts.HIV/MTB coinfection is more complex than a single infection,and the interaction between the two diseases aggravates the deterioration caused by the disease,resulting in increased hospitalizations and deaths.Rapid screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in HIV/MTB coinfected individuals,thereby reducing transmission and the incidence of adverse prognoses.To date,pathogenic detection has remained the gold standard for diagnosing tuberculosis,but its sensitivity and specificity are greatly affected by the body's immune status,which limits its application in the diagnosis of HIV/MTB coinfection.Recently,immunology and molecular detection technology has developed rapidly.New detection technologies,such as interferon-γ release assays,interferon-gamma inducible protein 10,and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods,significantly improved the sensitivity and specificity of tuberculosis diagnosis,and brought new hope to the detection of HIV/MTB coinfection.In this article,the principle,scope of application,and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of HIV/MTB coinfection.展开更多
Animal-derived biological products, such as fetal bovine serum(FBS) and trypsin, are important supplements for scientific, pharmaceutical, and medical use. Although preventive guidelines and tests are implemented to r...Animal-derived biological products, such as fetal bovine serum(FBS) and trypsin, are important supplements for scientific, pharmaceutical, and medical use. Although preventive guidelines and tests are implemented to reduce potential viral contamination in these biologicals, they do not target unusual or emerging viruses, leading to safety concerns. Using unbiased metagenomics, we investigated the presence of viruses in recently collected commercial FBS and trypsin samples from different geographic regions. In total, we detected viralsequencesbelongingto Parvoviridae,Anelloviridae,Flaviviridae,Herpesviridae,Caliciviridae, Nodaviridae, Rhabdoviridae, and Paramyxoviridae, including several viruses related to bovine diseases, viruses of potential human and insect origin, and viruses of unknown origin. Bovine parvovirus 3 and bosavirus were detected with high frequency and abundance in FBS, necessitating more stringent testing for these parvoviruses during production. Both bovine norovirus and bovine viral diarrhea virus 1 displayed relatively high genetic distance to closest hits, indicating the presence of new genotypes in farm animals. While the origin of novel lyssavirus and Nipah virus is unclear, their presence raises the possibility of the introduction of pathogenic animal-derived viruses into biologicals.Our results showed relatively widespread contamination of different viruses in biologicals,underscoring the need for robust safety protocol alternatives, such as metagenomic sequencing, to monitor emerging viruses.展开更多
During acute human immunodeficiency virus(HIV)infection,depletion of CD4^(+) T cells in the host gut mucosa occurs prior to its occurrence in the peripheral blood and other lymphoid tissues.Expression of integrinα4β...During acute human immunodeficiency virus(HIV)infection,depletion of CD4^(+) T cells in the host gut mucosa occurs prior to its occurrence in the peripheral blood and other lymphoid tissues.Expression of integrinα4β7,a gut-homing receptor on CD4^(+) T cells,not only provides a potential receptor for HIV but also plays a critical role in lymphocyte migration from the circulation to the intestine.In our previous study,it was found that circulating gut-homingα4β7 CD4^(+) T cells,including the Th17 and Th1 subsets,were significantly depleted during acute HIV-1 infection.1 Moreover,no gut-homing Treg cells were depleted.Thus,the gut-homing Treg:Th17 ratio was inversely correlated with the CD4 T+cell count.展开更多
Introduction In December 2019,multiple cases of aggravated pneumonia of unidentified origin were reported inWuhan,China.These were confirmed to be caused by a novel coronavirus.The World Health Organization(WHO)named ...Introduction In December 2019,multiple cases of aggravated pneumonia of unidentified origin were reported inWuhan,China.These were confirmed to be caused by a novel coronavirus.The World Health Organization(WHO)named the disease coronavirus disease 2019(COVID-19).The International Committee on Taxonomy of Viruses officially identified the novel virus severe acute respiratory syndrome coronavirus 2(SARSCoV-2).[1]Although China is now a low endemic areawith a downward trend in the number of confirmed and suspected cases,[2]the threat of the COVID-19 pandemic remains critical.By mid-March 2022,the cumulative number of reported confirmed cases of COVID-19 worldwide exceeded 450 million,with more than 6 million deaths.[3]Since there is no specific therapeutic drug for the treatment of COVID-19,it is important to control the epidemic by actively promoting SARS-CoV-2 vaccination globally,reducing the risk of viral transmission and the incidence of severe COVID-19,thus improving prognoses.[4]展开更多
Background:Total human immunodeficiency virus(HIV)DNA and integrated HIV DNA are widely used markers of HIV persistence.Droplet digital polymerase chain reaction(ddPCR)can be used for absolute quantification without n...Background:Total human immunodeficiency virus(HIV)DNA and integrated HIV DNA are widely used markers of HIV persistence.Droplet digital polymerase chain reaction(ddPCR)can be used for absolute quantification without needing a standard curve.Here,we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods:The limit of detection,dynamic ranges,sensitivity,and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat(LTR)and human CD3 gene(for total HIV DNA)and ACH-2 cells(for integrated HIV DNA).Forty-two cases on stable suppressive antiretroviral therapy(ART)were assayed in total HIV DNA and integrated HIV DNA.Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive(CD4^(+))T-cell counts,CD8^(+)T-cell counts and CD4/CD8 T-cell ratio,respectively.The assay linear dynamic range and lower limit of detection(LLOD)were also assessed.Results:The assay could detect the presence of HIV-1 copies 100%at concentrations of 6.3 copies/reaction,and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction(95%confidence intervals[CI]:3.6-6.5 copies/reaction)with linearity over a 5-log_(10)-unit range in total HIV DNA assay.For the integrated HIV DNA assay,the LLOD was 8.0 copies/reaction(95%CI:5.8-16.6 copies/reaction)with linearity over a 3-log 10-unit range.Total HIV DNA in CD4^(+)T cells was positively associated with integrated HIV DNA(r=0.76,P<0.0001).Meanwhile,both total HIV DNA and integrated HIV DNA in CD4^(+)T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8^(+)T-cell counts.Conclusions:This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity.It can be readily adapted for measuring HIV DNA with non-B clades,and it could be beneficial for testing in clinical trials.展开更多
Integrase strand transfer inhibitors(INSTIs)have emerged as the first‐line choice for treating human immunodeficiency virus(HIV)infection due to their superior efficacy and safety.However,the impact of INSTIs on the ...Integrase strand transfer inhibitors(INSTIs)have emerged as the first‐line choice for treating human immunodeficiency virus(HIV)infection due to their superior efficacy and safety.However,the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV(PLWH)is not fully understood due to limited data.In this study,we conducted a cross‐sectional examination of PLWH receiving antiretroviral therapy,with a specific focus on HIV‐positive men who have sex with men(MSM)on INSTI‐based regimens(n=61)and efavirenz(EFV)‐based regimens(n=28).Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging(MRI)scans,including T1‐weighted images and resting‐state functional MRI.Compared to the EFV group,the INSTI group exhibited primarily reduced gray matter volume(GMV)in the right superior parietal gyrus,higher regional homogeneity(ReHo)in the left postcentral gyrus,lower ReHo in the right orbital part of the inferior frontal gyrus,and increased voxel‐wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus.Furthermore,the analysis revealed a main effect of antiretroviral drugs on GMV changes,but no main effect of neuropsychiatric disorders or their interaction.The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group,validating the initial findings.Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI‐based regimens compared to those on EFV‐based regimens.These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI‐based regimens。展开更多
Introduction:A novel recombinant antigen-based capture enzyme immunoassay(RAg-CEIA)was optimized and used to determine technical parameters for estimating human immunodeficiency virus type 1(HIV-1)incidence in China.M...Introduction:A novel recombinant antigen-based capture enzyme immunoassay(RAg-CEIA)was optimized and used to determine technical parameters for estimating human immunodeficiency virus type 1(HIV-1)incidence in China.Methods:We employed orthogonal experimental design to optimize RAg-CEIA by adjusting raw material dilution ratios.The assay was used to measure normalized optical density(ODn)values in 171 longitudinal plasma specimens from 51 HIV-1 seroconverting individuals,plotted against estimated days post-seroconversion.We determined the optimal ODn threshold value for differentiating recent from long-term infections and calculated the mean duration of recent infection(MDRI)for incidence estimation.The false recent rate(FRR)was determined using 481 HIV-1 antibody-positive specimens with infection durations exceeding twice the MDRI.Results:Optimal RAg-CEIA parameters were established with a raw material dilution ratio of 1/12 for calibrator preparation and an enzyme conjugate titer of 1:1200.ODn values demonstrated consistent temporal increases across HIV-1 seroconverting individuals,though with notable kinetic heterogeneity in individual responses.The optimal ODn threshold value of 0.8 for distinguishing recent from long-term infections corresponded to an MDRI of 205 days and an FRR of 4.78%.Conclusions:The optimized RAg-CEIA effectively differentiates recent from long-term HIV-1 infections at the population level,enabling reliable HIV-1 incidence estimation in China.展开更多
The purpose of vaccination is to generate Neutralizing antibodies(NAbs),as these antibodies have neutralizing activity against viral infections such as HIV and SARS-CoV-2.NAb has high antiviral potency and therefore b...The purpose of vaccination is to generate Neutralizing antibodies(NAbs),as these antibodies have neutralizing activity against viral infections such as HIV and SARS-CoV-2.NAb has high antiviral potency and therefore be served as therapeutics.However,induction of NAb is not easy,and RNA viruses such as HIV and SARS-CoV-2 always escape NAb binding epitopes due to the rapid mutation of their genomes.Thus,despite Fab and neutralizing,other component and its function against viral infection is important in the biology of antibodies,such as the Fc part in antibodies.Fc-mediated function showed protective potency in viral infection.Fc-mediated ADCC contributes to protect against HIV in phase II/III clinical trial,but remains controversy.Marginal evidences show protectivity of non-NAb and Fc-mediated ADCC in HIV infection and AIDS progress.In SARS-CoV-2 infection,Fc-mediated ADCC showed potent antiviral activity as well.While,the participation of non-NAb is elusive in the control of HIV and SARS-CoV-2 dual infection.Limited data reported that Fc-mediated functions is regulated following HIV infection as people living with HIV after vaccination of pulmonary pathogens display increased ADCC activity to homologues pathogens.In order to reveal Fc-mediated function,there is a need to actively develop a robust and accurate in vitro assay to measure it.This is an emerging attract that have drawn much attention.展开更多
Background: A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for deci...Background: A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for decision-making related to HIV prevention and control. The variances in these indices between different population groups, genders, and ages are critical to decipher evolving patterns of the HIV epidemic in specific populations.Methods: A secondary analysis of relevant data was conducted using data extracted from the Global Burden of Disease study of 2019. HIV/acquired immune deficiency syndrome (AIDS) incidence, prevalence, AIDS-related mortality, and mortality-to-prevalence ratio (MPR) for annual percentage change, average annual percentage change (AAPC), and corresponding 95% confidence intervals (CIs) were calculated using joinpoint regression statistical analysis.Results: The AAPC of HIV/AIDS incidence, prevalence, AIDS-related mortality rate, and MPR were -1.4 (95% CI: -1.6, -1.2), 4.1 (95% CI: 4.0, 4.3), 2.0 (95% CI: 1.7, 2.3), and -2.1 (95% CI: -2.3, -1.8) between 1990 and 2019 globally, and were 3.5 (95% CI: 2.2, 4.8), 6.9 (95% CI: 6.8, 7.0), 8.1 (95% CI: 7.1, 9.1), and 1.2 (95% CI: 0.1, 2.3) in China during the same period. In terms of differences in the preceding indicators by gender, we observed a similar pattern of trends for male and female genders both globally and in China during the entire study period. Each specific age group exhibits a distinct pattern in terms of incidence, prevalence, mortality rate, and MPR both globally and in China.Conclusions: Prevalence and mortality rates of HIV/AIDS have increased between 1990 and 2019 globally and in China. While the incidence rate and MPR have declined globally over the past three decades, these two indicators are observed to present an increasing trend in China. There is a high HIV burden among young and middle-aged adults globally;however, the elderly have a high HIV burden in China. HIV screening at older age should be scaled up, and patients with advanced HIV disease should be provided early with additional care and health resources.展开更多
Preferential infection and depletion of gut-homing a4β7 CD4＋ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing a4p7 CD4＋ T cells and their functional subsets during th...Preferential infection and depletion of gut-homing a4β7 CD4＋ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing a4p7 CD4＋ T cells and their functional subsets during the acute stages of HIV-1 infection are less documented. Therefore, we conducted a cohort study to investigate whether acute HIV-1 infection induced abnormalities in gut-homing a4β7 CD4＋ T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing a4β7 CD4＋ T cells in 26 acute HIV-l-infected patients compared with 20 healthy individuals. We found that circulating gut-homing a4β7 CD4＋ T cells were preferentially depleted during acute HIV-1 infection and were positively correlated with absolute CD4＋ T-cell count in blood. Notably, Th17 and Thl cell subsets of gut-homing CD4＋ T cells were also decreased, which resulted in an imbalance of T helper cells （Th 1）-regulatory T cells （Treg） and Treg.Th 17 ratios. Gut-homing Th17 and Thl cells were also positively correlated with the absolute number of total CD4＋ T cells and gut-homing CD4＋ T cells. The gut-homing Treg：Th17 ratio was inversely correlated with the CD4＋ T-cell count. Taken together, the analyses of our acute HIV-1 cohort demonstrate that gut-homing a4β7 CD4＋ T cells and their functional subsets were profoundly depleted during acute HIV-1 infection, which may have resulted in the persistent loss of circulating CD4＋ T cells and an imbalance of Thl-Treg and Treg.Th17 ratios and contribute to HIV-1 disease pathogenesis.展开更多
Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(l...Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(+)CD8^(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI(r=-0.578,P=0.015).Notably,in the first month of AHI,few CD3^(+)CD8^(low) T cells,but comparable amounts of CD3^(+)CD8^(high) T cells,responded to Gag peptides.Then,weaker HIV-1-specific T-cell responses were induced in CD3^(+)CD8^(low) T cells than CD3^(+)CD8^(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3^(+)CD8^(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response.Subsequently,CD3^(+)CD8^(low) T-cell number decreased gradually as infection persisted,and their anti-HIV functions were inferior to those of CD3^(+)CD8^(high) T cells.展开更多
Antiretroviral therapy against human immunodeficiency virus (HIV) is effective in controlling viral replication but cannot completely eliminate HIV due to the persistence of the HIV reservoir. Innate and adaptive immu...Antiretroviral therapy against human immunodeficiency virus (HIV) is effective in controlling viral replication but cannot completely eliminate HIV due to the persistence of the HIV reservoir. Innate and adaptive immune responses have been proposed to contribute to preventing HIV acquisition, controlling HIV replication and eliminating HIV-infected cells. However, the immune responses naturally induced in HIV-infected individuals rarely eradicate HIV infection, which may be caused by immune escape, an inadequate magnitude and breadth of immune responses, and immune exhaustion. Optimizing these immune responses may solve the problems of epitope escape and insufficient sustained memory responses. Moreover, immune interventions aimed at improving host immune response can reduce HIV reservoirs, which have become one focus in the development of innovative strategies to eliminate HIV reservoirs. In this review, we focus on the immune response against HIV and how antiviral immune responses affect HIV reservoirs. We also discuss the development of innovative strategies aiming to eliminate HIV reservoirs and promoting functional cure of HIV infection.展开更多
A massive depletion of CD4+T lymphocytes has been described in early and acute human immunodeficiency virus(HIV)infection,leading to an imbalance between the human microbiome and immune responses.In recent years,a gro...A massive depletion of CD4+T lymphocytes has been described in early and acute human immunodeficiency virus(HIV)infection,leading to an imbalance between the human microbiome and immune responses.In recent years,a growing interest in the alterations in gut microbiota in HIV infection has led to many studies;however,only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals.Evidence has indicated the dysbiosis of oral microbiota in people living with HIV(PLWH).Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals,including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells.As a result,disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses,which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities.Although the introduction of antiretroviral therapy(ART)has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals,the dysbiosis in oral microbiome persists.Furthermore,several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing.However,the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear.In this article,we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases.We also discuss how ART and probiotics influence the oral microbiome in HIV infection.We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.展开更多
Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and ...Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and antitumor activity.However,it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inactivated vaccines.Methods:Forty-five people living with HIV(PLWH)on antiretroviral therapy(ART)for more than two years and 31 healthy controls(HCs),all received a third dose of a SARS-CoV-2 inactivated vaccine,were enrolled in this study.The amounts,activation,proportion of cell subsets,and magnitude of the SARS-CoV-2-specific immune response of TIGIT^(+)CD4^(+)and TIGIT^(+)CD8^(+)T cells were investigated before the third dose but 6 months after the second vaccine dose(0W),4 weeks(4W)and 12 weeks(12W)after the third dose.Results:Compared to that in HCs,the frequency of TIGIT^(+)CD8^(+)T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine,and the immune activation of TIGIT^(+)CD8^(+)T cells also increased.A decrease in the ratio of both T naïve(T_(N))and central memory(T_(CM))cells among TIGIT^(+)CD8^(+)T cells and an increase in the ratio of the effector memory(T_(EM))subpopulation were observed at 12W in PLWH.Interestingly,particularly at 12W,a higher proportion of TIGIT^(+)CD8^(+)T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay.Compared with 0W,SARS-CoV-2-specific TIGIT^(+)CD8^(+)T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs.Additionally,at all time points,the SARS-CoV-2-specific responses of TIGIT^(+)CD8^(+)T cells in PLWH were significantly weaker than those of TIGIT-CD8^(+)T cells.However,in HCs,the difference in the SARS-CoV-2-specific responses induced between TIGIT^(+)CD8^(+)T cells and TIGIT-CD8^(+)T cells was insignificant at 4W and 12W,except at 0W.Conclusions:TIGIT expression on CD8^(+)T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine,suggesting weakened resistance to SARS-CoV-2 infection,especially in PLWH.Furthermore,TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8^(+)T cells,thereby enhancing the effectiveness of vaccination.展开更多
Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection.However,it was unknown whether SARS-CoV-2 ...Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection.However,it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer(NK)cell response in people living with human immunodeficiency virus(PLWH)and healthy individuals.Methods:Forty-seven PLWH and thirty healthy controls(HCs)inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study.The effect of SARS-CoV-2 vaccine on NK cell frequency,phenotype,and function in PLWH and HCs was evaluated by flow cytometry,and the response of NK cells to SARS-CoV-2 Omicron Spike(SARS-2-OS)protein stimulation was also evaluated.Results:SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH,which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine.However,in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers.Additionally,the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0,4 and 12 weeks,but the percentage of CD16^(+)NK cells in PLWH was significantly higher than that in HCs at 2,4 and 12 weeks after the third dose of vaccine.Interestingly,the frequency of CD16^(+)NK cells was significantly negatively correlated with the proportion of CD107a^(+)NK cells in PLWH at each time point after the third dose.Similarly,this phenomenon was also observed in HCs at 0,2,and 4 weeks after the third dose.Finally,regardless of whether NK cells were stimulated with SARS-2-OS or not,we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.Conclusions:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells,indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.展开更多
Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(HIV)-infected individuals,ART alone cannot completely eliminate HIV due to its integra...Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(HIV)-infected individuals,ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs.To achieve a functional cure for HIV infection,numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART.Early studies have tested adoptive T-cell therapies in HIV-infected individuals,but their effectiveness was limited.In recent years,with the technological progress and great success of chimeric antigen receptor(CAR)therapy in the treatment of hematological malignancies,CAR therapy has gradually shown its advantages in the field of HIV infection.Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells.Therefore,CAR therapy may be beneficial for enhancing HIV immunity,achieving HIV control,and eliminating HIV reservoirs,gradually becoming a promising strategy for achieving a functional HIV cure.In this review,we provide an overview of the design of anti-HIV CAR proteins,the cell types of anti-HIV CAR(including CAR T cells,CAR natural killer cells,and CAR-encoding hematopoietic stem/progenitor cells),the clinical application of CAR therapy in HIV infection,and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.展开更多
To the Editor:Immune non-responders(INRs),who account for approximately 10-40%of human immunodeficiency virus(HIV)-infected individuals,have received effective treatment and exhibit persistent suppression of viral rep...To the Editor:Immune non-responders(INRs),who account for approximately 10-40%of human immunodeficiency virus(HIV)-infected individuals,have received effective treatment and exhibit persistent suppression of viral replication,but their CD4^(+)T-cell counts are not restored.They are likely to have an increased risk of non-acquired immunodeficiency syndrome(AIDS)-related morbidity and mortality compared with immune responders(IRs).[1]CD8^(+)T cells play an important role in viral infection,and the functional properties of circulating CD8^(+)T cells have been associated with immune control of HIV.High CD8^(+)T-cell counts are beneficial for persistent viral decay and CD4 T-cell recovery in immune-restored patients during long-term antiretroviral therapy(ART).[2]Two subsets of CD8^(+)T cells have been identified according to their intensity of CD8 expression:CD8^(bri)and CD8^(dim)T lymphocytes.It was demonstrated that CD3^(+)CD8^(dim)T cells,with weaker function than CD3^(+)CD8^(bri)T cells,were associated with disease progression during HIV infection.[3]However,dynamic changes in the numbers of CD8^(bri)and CD8^(dim)T cells in INRs and IRs before and after ART have not yet been reported.展开更多
Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemi...Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemic lupus erythematosus (cSLE) are limited. Therefore, this study aimed to investigate circEPSTI1 expression in cSLE and evaluate its potential as a biomarker for diagnosing cSLE.Methods:This study included 70 children diagnosed with cSLE, 20 diagnosed with juvenile idiopathic arthritis (JIA), 20 diagnosed with juvenile dermatomyositis (JDM), and 50 healthy children at the Rheumatology Department of Beijing Children's Hospital from January 2019 to December 2019. Quantitative polymerase chain reaction was used to determine circEPSTI1 expression in the children. Correlations between circEPSTI1 and clinical features were assessed using Spearman's correlation test. Additionally, we calculated the receiver operating characteristic curve to assess the diagnostic efficacy.Results:We found that circEPSTI1 expression was higher in children with cSLE (4.62 ± 3.55) than that in healthy children (1.00 ± 0.45), those with JDM (1.06 ± 0.76), and those with JIA (0.96 ± 0.48). The area of the curve of circEPSTI1 was 0.892 (95% confidence interval [CI]: 0.832-0.952, p < 0.001) to discriminate children with SLE from healthy children, with a specificity of 0.814 and a sensitivity of 0.922. Children with lupus nephritis showed a higher circEPSTI1 expression than healthy children, those with JDM, and those with JIA. In addition, circEPSTI1 expression in children with SLE showed significant correlations with the SLE Disease Activity Index ( p < 0.0001) and C3 concentrations ( p = 0.001). Conclusion:Our study suggests that circEPSTI1 is a promising biomarker for the diagnosis and monitoring of cSLE.展开更多
Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thou...Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency.The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system.Specifically,MPXV employs unique immune evasion strategies against a wide range of immunological elements,presenting a considerable challenge for treatment,especially following the discontinuation of routine smallpox vaccination among the general population.In this review,we start by discussing the entry of the mpox virus and the onset of early infection,followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses.Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection.With respect to adaptive immunity,mpox viruses exhibit unique and exceptional T-cell inhibition capabilities,thereby comprehensively remodeling the host immune environment.The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system.The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating.Finally,we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development.This review may provide valuable information for the development of new immunological treatments for mpox.展开更多
Importance:Systemic lupus erythematosus(SLE)is a diffuse connective tissue disease with complex clinical manifestations and prolonged course.The early diagnosis and condition monitoring of SLE are crucial to disease p...Importance:Systemic lupus erythematosus(SLE)is a diffuse connective tissue disease with complex clinical manifestations and prolonged course.The early diagnosis and condition monitoring of SLE are crucial to disease prognosis.Objective:To assess the diagnostic value of long noncoding RNA(lncRNA)nuclear enriched abundant transcript 1(NEAT1)in childhood-onset SLE(cSLE).Methods:Fifty-seven children diagnosed with SLE,40 children diagnosed with juvenile idiopathic arthritis(JIA),and 40 healthy children were included.Peripheral blood samples from each patient were collected.A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood.Associations among parameters were analyzed using the Mann-Whitney U test or independent sample t-test.Results:The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA.Receiver operating characteristic curves revealed an area under the curve(AUC)of 0.633(95%confidence interval[CI],0.524-0.742;P=0.024)for lncNEAT1_1.The AUC of lncNEAT1_2 was 0.812(95%CI,0.727-0.897;P<0.0001)to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925.Moreover,lncNEAT1_2 expression was higher in patients with cSLE presenting with fever,lupus nephritis,elevated erythrocyte sedimentation rate,active disease activity,and decreased C3 level,compared with those without these conditions.However,no similar correlation was observed for lncNEAT1_1.Interpretation:The expression of lncNEAT1_2 was significantly elevated in children with SLE,especially those with fever,renal involvement,and low C3 levels.These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.展开更多
基金the Beijing Natural Science Foundation(Z220018)the Belt and Road International Health Cooperation Project of Beijing Municipal Health Commission,the National Key R&D Program of China(2023YFE0116000,2023YFC2308300,2023YFC2308302)+1 种基金the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018,2022-1-007)the Beijing Key Laboratory for HIV/AIDS Research(BZ0089).The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘The high morbidity and mortality rate of individuals with human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)coinfected with Mycobacterium tuberculosis(MTB)is a tough challenge for current global tuberculosis prevention and control efforts.HIV/MTB coinfection is more complex than a single infection,and the interaction between the two diseases aggravates the deterioration caused by the disease,resulting in increased hospitalizations and deaths.Rapid screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in HIV/MTB coinfected individuals,thereby reducing transmission and the incidence of adverse prognoses.To date,pathogenic detection has remained the gold standard for diagnosing tuberculosis,but its sensitivity and specificity are greatly affected by the body's immune status,which limits its application in the diagnosis of HIV/MTB coinfection.Recently,immunology and molecular detection technology has developed rapidly.New detection technologies,such as interferon-γ release assays,interferon-gamma inducible protein 10,and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods,significantly improved the sensitivity and specificity of tuberculosis diagnosis,and brought new hope to the detection of HIV/MTB coinfection.In this article,the principle,scope of application,and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of HIV/MTB coinfection.
基金supported by the National Natural Science Foundation of China (32170147,31900158)。
文摘Animal-derived biological products, such as fetal bovine serum(FBS) and trypsin, are important supplements for scientific, pharmaceutical, and medical use. Although preventive guidelines and tests are implemented to reduce potential viral contamination in these biologicals, they do not target unusual or emerging viruses, leading to safety concerns. Using unbiased metagenomics, we investigated the presence of viruses in recently collected commercial FBS and trypsin samples from different geographic regions. In total, we detected viralsequencesbelongingto Parvoviridae,Anelloviridae,Flaviviridae,Herpesviridae,Caliciviridae, Nodaviridae, Rhabdoviridae, and Paramyxoviridae, including several viruses related to bovine diseases, viruses of potential human and insect origin, and viruses of unknown origin. Bovine parvovirus 3 and bosavirus were detected with high frequency and abundance in FBS, necessitating more stringent testing for these parvoviruses during production. Both bovine norovirus and bovine viral diarrhea virus 1 displayed relatively high genetic distance to closest hits, indicating the presence of new genotypes in farm animals. While the origin of novel lyssavirus and Nipah virus is unclear, their presence raises the possibility of the introduction of pathogenic animal-derived viruses into biologicals.Our results showed relatively widespread contamination of different viruses in biologicals,underscoring the need for robust safety protocol alternatives, such as metagenomic sequencing, to monitor emerging viruses.
文摘During acute human immunodeficiency virus(HIV)infection,depletion of CD4^(+) T cells in the host gut mucosa occurs prior to its occurrence in the peripheral blood and other lymphoid tissues.Expression of integrinα4β7,a gut-homing receptor on CD4^(+) T cells,not only provides a potential receptor for HIV but also plays a critical role in lymphocyte migration from the circulation to the intestine.In our previous study,it was found that circulating gut-homingα4β7 CD4^(+) T cells,including the Th17 and Th1 subsets,were significantly depleted during acute HIV-1 infection.1 Moreover,no gut-homing Treg cells were depleted.Thus,the gut-homing Treg:Th17 ratio was inversely correlated with the CD4 T+cell count.
基金supported by the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018)the Ministry of Science and Technology of China(CPL-1233)+3 种基金the National Natural Science Foundation of China(NSFC,81974303)the“Climbing the peak(Dengfeng)”Talent Training Program of Beijing Hospitals Authority(DFL20191701)the Beijing Health Technologies Promotion Program(BHTPP2020)the Beijing Key Laboratory for HIV/AIDS Research(BZ0089).
文摘Introduction In December 2019,multiple cases of aggravated pneumonia of unidentified origin were reported inWuhan,China.These were confirmed to be caused by a novel coronavirus.The World Health Organization(WHO)named the disease coronavirus disease 2019(COVID-19).The International Committee on Taxonomy of Viruses officially identified the novel virus severe acute respiratory syndrome coronavirus 2(SARSCoV-2).[1]Although China is now a low endemic areawith a downward trend in the number of confirmed and suspected cases,[2]the threat of the COVID-19 pandemic remains critical.By mid-March 2022,the cumulative number of reported confirmed cases of COVID-19 worldwide exceeded 450 million,with more than 6 million deaths.[3]Since there is no specific therapeutic drug for the treatment of COVID-19,it is important to control the epidemic by actively promoting SARS-CoV-2 vaccination globally,reducing the risk of viral transmission and the incidence of severe COVID-19,thus improving prognoses.[4]
基金supported by the National Key R&D Program of China(Nos.2021YFC2301900 and 2021YFC2301905)the National 13th Five-Year Grand Program on Key Infectious Disease Control(Nos.2018ZX10301-101 and 2018ZX10301101-001-001)+3 种基金the National Natural Science Foundation of China(Nos.82241072,82072271,and 82272319)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(Nos.2022-2-018 and 2022-1-007)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(No.DFL20191701)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089).
文摘Background:Total human immunodeficiency virus(HIV)DNA and integrated HIV DNA are widely used markers of HIV persistence.Droplet digital polymerase chain reaction(ddPCR)can be used for absolute quantification without needing a standard curve.Here,we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods:The limit of detection,dynamic ranges,sensitivity,and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat(LTR)and human CD3 gene(for total HIV DNA)and ACH-2 cells(for integrated HIV DNA).Forty-two cases on stable suppressive antiretroviral therapy(ART)were assayed in total HIV DNA and integrated HIV DNA.Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive(CD4^(+))T-cell counts,CD8^(+)T-cell counts and CD4/CD8 T-cell ratio,respectively.The assay linear dynamic range and lower limit of detection(LLOD)were also assessed.Results:The assay could detect the presence of HIV-1 copies 100%at concentrations of 6.3 copies/reaction,and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction(95%confidence intervals[CI]:3.6-6.5 copies/reaction)with linearity over a 5-log_(10)-unit range in total HIV DNA assay.For the integrated HIV DNA assay,the LLOD was 8.0 copies/reaction(95%CI:5.8-16.6 copies/reaction)with linearity over a 3-log 10-unit range.Total HIV DNA in CD4^(+)T cells was positively associated with integrated HIV DNA(r=0.76,P<0.0001).Meanwhile,both total HIV DNA and integrated HIV DNA in CD4^(+)T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8^(+)T-cell counts.Conclusions:This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity.It can be readily adapted for measuring HIV DNA with non-B clades,and it could be beneficial for testing in clinical trials.
基金supported by the National Natural Science Foundation of China(82072271,82241072,82072294)the National Key Research and Development Program of China(2021YFC2501402,2021YFC0122601)+8 种基金the Beijing Natural Science Foundation(7222095,7222091)the Peak Talent Program of Beijing Hospital Authority(DFL20191701)the Capital’s Funds for Health Improvement and Research(2022-1-1151)the Research and Translational Application of Clinical Characteristic Diagnostic and Treatment Techniques in Capital City(Z221100007422055)the Beijing Research Center for Respiratory Infectious Diseases(BJRID2024-001)the Beijing Hospitals Authority Innovation Studio of Young Staff Funding Support(2021037)the High-level Public Health Technical Personnel Construction Project(2022-1-007)the High-level Public Health Specialized Talents Project of Beijing Municipal Health commission(2022-02-20)the Beijing Key Laboratory for HIV/AIDS Research(BZ0089).
文摘Integrase strand transfer inhibitors(INSTIs)have emerged as the first‐line choice for treating human immunodeficiency virus(HIV)infection due to their superior efficacy and safety.However,the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV(PLWH)is not fully understood due to limited data.In this study,we conducted a cross‐sectional examination of PLWH receiving antiretroviral therapy,with a specific focus on HIV‐positive men who have sex with men(MSM)on INSTI‐based regimens(n=61)and efavirenz(EFV)‐based regimens(n=28).Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging(MRI)scans,including T1‐weighted images and resting‐state functional MRI.Compared to the EFV group,the INSTI group exhibited primarily reduced gray matter volume(GMV)in the right superior parietal gyrus,higher regional homogeneity(ReHo)in the left postcentral gyrus,lower ReHo in the right orbital part of the inferior frontal gyrus,and increased voxel‐wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus.Furthermore,the analysis revealed a main effect of antiretroviral drugs on GMV changes,but no main effect of neuropsychiatric disorders or their interaction.The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group,validating the initial findings.Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI‐based regimens compared to those on EFV‐based regimens.These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI‐based regimens。
基金Supported by the National Science and Technology Major Project of the 13th Five-year Plan(grants 2017ZX10201101-002-003 and 2018ZX10721102-003-002)。
文摘Introduction:A novel recombinant antigen-based capture enzyme immunoassay(RAg-CEIA)was optimized and used to determine technical parameters for estimating human immunodeficiency virus type 1(HIV-1)incidence in China.Methods:We employed orthogonal experimental design to optimize RAg-CEIA by adjusting raw material dilution ratios.The assay was used to measure normalized optical density(ODn)values in 171 longitudinal plasma specimens from 51 HIV-1 seroconverting individuals,plotted against estimated days post-seroconversion.We determined the optimal ODn threshold value for differentiating recent from long-term infections and calculated the mean duration of recent infection(MDRI)for incidence estimation.The false recent rate(FRR)was determined using 481 HIV-1 antibody-positive specimens with infection durations exceeding twice the MDRI.Results:Optimal RAg-CEIA parameters were established with a raw material dilution ratio of 1/12 for calibrator preparation and an enzyme conjugate titer of 1:1200.ODn values demonstrated consistent temporal increases across HIV-1 seroconverting individuals,though with notable kinetic heterogeneity in individual responses.The optimal ODn threshold value of 0.8 for distinguishing recent from long-term infections corresponded to an MDRI of 205 days and an FRR of 4.78%.Conclusions:The optimized RAg-CEIA effectively differentiates recent from long-term HIV-1 infections at the population level,enabling reliable HIV-1 incidence estimation in China.
基金funded by the National Key R&D Program of China(2023YFE0116000)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018)+5 种基金Beijing Key Laboratory for HIV/AIDS Research(BZ0089)ANRS(Agence Nationale de Recherches sur le SIDA et les hépatites virales),the Investissements d’Avenir program managed by the ANR under reference ANR-10-LABX-77 and EHVA(N°681032,Horizon 2020)supported by the Strasbourg’s Interdisciplinary Thematic Institute(ITI)for Precision Medicine,TRANSPLANTEX NG,as part of the ITI 2021-2028 program of the University of Strasbourg,CNRS and INSERMfunded by IdEx Unistra[ANR-10-IDEX-0002]and SFRI-STRAT’US[ANR-20-SFRI-0012]the European regional development fund(European Union)INTERREG V program(project Personalis)MSD-Avenir grant AUTOGEN,for their financial supports.
文摘The purpose of vaccination is to generate Neutralizing antibodies(NAbs),as these antibodies have neutralizing activity against viral infections such as HIV and SARS-CoV-2.NAb has high antiviral potency and therefore be served as therapeutics.However,induction of NAb is not easy,and RNA viruses such as HIV and SARS-CoV-2 always escape NAb binding epitopes due to the rapid mutation of their genomes.Thus,despite Fab and neutralizing,other component and its function against viral infection is important in the biology of antibodies,such as the Fc part in antibodies.Fc-mediated function showed protective potency in viral infection.Fc-mediated ADCC contributes to protect against HIV in phase II/III clinical trial,but remains controversy.Marginal evidences show protectivity of non-NAb and Fc-mediated ADCC in HIV infection and AIDS progress.In SARS-CoV-2 infection,Fc-mediated ADCC showed potent antiviral activity as well.While,the participation of non-NAb is elusive in the control of HIV and SARS-CoV-2 dual infection.Limited data reported that Fc-mediated functions is regulated following HIV infection as people living with HIV after vaccination of pulmonary pathogens display increased ADCC activity to homologues pathogens.In order to reveal Fc-mediated function,there is a need to actively develop a robust and accurate in vitro assay to measure it.This is an emerging attract that have drawn much attention.
基金Joint Medical Research Projects of Chongqing Municipal Health Committee and Chongqing Municipal Science and Technology Bureau(Nos.2022QNXM032, 2020FYYX066, 2020MSXM097, and 2020FYYX118)Chongqing Science and Technology Bureau(No. cstc2020jscx-cylhX0001)Chongqing Talent Cultivation Program(No.cstc2021ycjh-bgzxm0275)。
文摘Background: A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for decision-making related to HIV prevention and control. The variances in these indices between different population groups, genders, and ages are critical to decipher evolving patterns of the HIV epidemic in specific populations.Methods: A secondary analysis of relevant data was conducted using data extracted from the Global Burden of Disease study of 2019. HIV/acquired immune deficiency syndrome (AIDS) incidence, prevalence, AIDS-related mortality, and mortality-to-prevalence ratio (MPR) for annual percentage change, average annual percentage change (AAPC), and corresponding 95% confidence intervals (CIs) were calculated using joinpoint regression statistical analysis.Results: The AAPC of HIV/AIDS incidence, prevalence, AIDS-related mortality rate, and MPR were -1.4 (95% CI: -1.6, -1.2), 4.1 (95% CI: 4.0, 4.3), 2.0 (95% CI: 1.7, 2.3), and -2.1 (95% CI: -2.3, -1.8) between 1990 and 2019 globally, and were 3.5 (95% CI: 2.2, 4.8), 6.9 (95% CI: 6.8, 7.0), 8.1 (95% CI: 7.1, 9.1), and 1.2 (95% CI: 0.1, 2.3) in China during the same period. In terms of differences in the preceding indicators by gender, we observed a similar pattern of trends for male and female genders both globally and in China during the entire study period. Each specific age group exhibits a distinct pattern in terms of incidence, prevalence, mortality rate, and MPR both globally and in China.Conclusions: Prevalence and mortality rates of HIV/AIDS have increased between 1990 and 2019 globally and in China. While the incidence rate and MPR have declined globally over the past three decades, these two indicators are observed to present an increasing trend in China. There is a high HIV burden among young and middle-aged adults globally;however, the elderly have a high HIV burden in China. HIV screening at older age should be scaled up, and patients with advanced HIV disease should be provided early with additional care and health resources.
文摘Preferential infection and depletion of gut-homing a4β7 CD4＋ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing a4p7 CD4＋ T cells and their functional subsets during the acute stages of HIV-1 infection are less documented. Therefore, we conducted a cohort study to investigate whether acute HIV-1 infection induced abnormalities in gut-homing a4β7 CD4＋ T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing a4β7 CD4＋ T cells in 26 acute HIV-l-infected patients compared with 20 healthy individuals. We found that circulating gut-homing a4β7 CD4＋ T cells were preferentially depleted during acute HIV-1 infection and were positively correlated with absolute CD4＋ T-cell count in blood. Notably, Th17 and Thl cell subsets of gut-homing CD4＋ T cells were also decreased, which resulted in an imbalance of T helper cells （Th 1）-regulatory T cells （Treg） and Treg.Th 17 ratios. Gut-homing Th17 and Thl cells were also positively correlated with the absolute number of total CD4＋ T cells and gut-homing CD4＋ T cells. The gut-homing Treg：Th17 ratio was inversely correlated with the CD4＋ T-cell count. Taken together, the analyses of our acute HIV-1 cohort demonstrate that gut-homing a4β7 CD4＋ T cells and their functional subsets were profoundly depleted during acute HIV-1 infection, which may have resulted in the persistent loss of circulating CD4＋ T cells and an imbalance of Thl-Treg and Treg.Th17 ratios and contribute to HIV-1 disease pathogenesis.
基金supported by grants from the National Natural Science Foundation of China(NSFC,81974303)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018)+7 种基金the Ministry of Science and Technology of China(CPL-1233)the“Climbing the peak(Dengfeng)”Talent Training Program of Beijing Hospitals Authority(DFL20191701 and DFL20181701)the Beijing Health Technologies Promotion Program(BHTPP2020)Beijing Key Laboratory for HIV/AIDS Research(BZ0089 and BZ0373)Beijing Natural Science Foundation(7191004)Beijing Municipal Science and Technology Project(Z211100002521024)the Natural Science Foundation of Capital Medical University(PYZ21126)and the Scientific Research Project of Beijing Youan Hospital(CCMU-2020-BJYAYY-2020YC-01 and CCMU-2021-YNKTXF2021001).
文摘Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(+)CD8^(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI(r=-0.578,P=0.015).Notably,in the first month of AHI,few CD3^(+)CD8^(low) T cells,but comparable amounts of CD3^(+)CD8^(high) T cells,responded to Gag peptides.Then,weaker HIV-1-specific T-cell responses were induced in CD3^(+)CD8^(low) T cells than CD3^(+)CD8^(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3^(+)CD8^(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response.Subsequently,CD3^(+)CD8^(low) T-cell number decreased gradually as infection persisted,and their anti-HIV functions were inferior to those of CD3^(+)CD8^(high) T cells.
基金This work was supported by grants from the National Natural Science Foundation of China (Nos. NSFC, 81974303 to BS, and 82072271 to TZ)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission (Nos. 2022-1-007 to TZ and 2022-2-018 to BS)+4 种基金the "Climbing the peak (Dengfeng) " Talent Training Program of Beijing Hospitals Authority (No. DFL20191701 to TZ)the Beijing Health Technologies Promotion Program (No. BHTPP2020 to TZ)the Beijing Key Laboratory for HIV/AIDS Research (No. BZ0089)the ANRS (Agence Nationale de Recherches sur le SIDA et les hépatites virales)the Investissements d’Avenir program managed by the ANR under reference ANR-10-LABX-77 and EHVA (No. 681032, Horizon 2020) .
文摘Antiretroviral therapy against human immunodeficiency virus (HIV) is effective in controlling viral replication but cannot completely eliminate HIV due to the persistence of the HIV reservoir. Innate and adaptive immune responses have been proposed to contribute to preventing HIV acquisition, controlling HIV replication and eliminating HIV-infected cells. However, the immune responses naturally induced in HIV-infected individuals rarely eradicate HIV infection, which may be caused by immune escape, an inadequate magnitude and breadth of immune responses, and immune exhaustion. Optimizing these immune responses may solve the problems of epitope escape and insufficient sustained memory responses. Moreover, immune interventions aimed at improving host immune response can reduce HIV reservoirs, which have become one focus in the development of innovative strategies to eliminate HIV reservoirs. In this review, we focus on the immune response against HIV and how antiviral immune responses affect HIV reservoirs. We also discuss the development of innovative strategies aiming to eliminate HIV reservoirs and promoting functional cure of HIV infection.
基金the National Natural Science Foundation of China(Nos.82072271,81772165,and 81974303)the National 13th Five-Year Grand Program on Key Infectious Disease Control(Nos.2017ZX10202101-004-001,2017ZX10202102-005-003)+1 种基金the NSFC-NIH Biomedical collaborative research program(No.81761128001)the Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)。
文摘A massive depletion of CD4+T lymphocytes has been described in early and acute human immunodeficiency virus(HIV)infection,leading to an imbalance between the human microbiome and immune responses.In recent years,a growing interest in the alterations in gut microbiota in HIV infection has led to many studies;however,only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals.Evidence has indicated the dysbiosis of oral microbiota in people living with HIV(PLWH).Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals,including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells.As a result,disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses,which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities.Although the introduction of antiretroviral therapy(ART)has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals,the dysbiosis in oral microbiome persists.Furthermore,several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing.However,the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear.In this article,we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases.We also discuss how ART and probiotics influence the oral microbiome in HIV infection.We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.
基金supported by Beijing Natural Science Foundation(No.L222068 to Bin Su)the National Natural Science Foundation of China(NSFC,No.82272319 to Hu Wu,and No.81974303 to Bin Su)+3 种基金the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(No.2022-2-018 to Bin Su,and No.2022-1-007 to Tong Zhang)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(No.DFL20191701 to Tong Zhang)the Beijing Health Technologies Promotion Program(No.BHTPP202002 to Tong Zhang)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089).
文摘Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and antitumor activity.However,it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inactivated vaccines.Methods:Forty-five people living with HIV(PLWH)on antiretroviral therapy(ART)for more than two years and 31 healthy controls(HCs),all received a third dose of a SARS-CoV-2 inactivated vaccine,were enrolled in this study.The amounts,activation,proportion of cell subsets,and magnitude of the SARS-CoV-2-specific immune response of TIGIT^(+)CD4^(+)and TIGIT^(+)CD8^(+)T cells were investigated before the third dose but 6 months after the second vaccine dose(0W),4 weeks(4W)and 12 weeks(12W)after the third dose.Results:Compared to that in HCs,the frequency of TIGIT^(+)CD8^(+)T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine,and the immune activation of TIGIT^(+)CD8^(+)T cells also increased.A decrease in the ratio of both T naïve(T_(N))and central memory(T_(CM))cells among TIGIT^(+)CD8^(+)T cells and an increase in the ratio of the effector memory(T_(EM))subpopulation were observed at 12W in PLWH.Interestingly,particularly at 12W,a higher proportion of TIGIT^(+)CD8^(+)T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay.Compared with 0W,SARS-CoV-2-specific TIGIT^(+)CD8^(+)T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs.Additionally,at all time points,the SARS-CoV-2-specific responses of TIGIT^(+)CD8^(+)T cells in PLWH were significantly weaker than those of TIGIT-CD8^(+)T cells.However,in HCs,the difference in the SARS-CoV-2-specific responses induced between TIGIT^(+)CD8^(+)T cells and TIGIT-CD8^(+)T cells was insignificant at 4W and 12W,except at 0W.Conclusions:TIGIT expression on CD8^(+)T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine,suggesting weakened resistance to SARS-CoV-2 infection,especially in PLWH.Furthermore,TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8^(+)T cells,thereby enhancing the effectiveness of vaccination.
基金supported by grants from the National Natural Science Foundation of China(Nos.82272319 and 82072271)Beijing Natural Science Foundation(No.L222068)+4 种基金the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(Nos.2022-2-018 and 2022-1-007)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(No.DFL20191701)the Beijing Health Technologies Promotion Program(No.BHTPP202002)Scientific Research Project of Beijing Youan Hospital-CCMU 2022(No.BJYAYY-YN-2022-18)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)
文摘Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection.However,it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer(NK)cell response in people living with human immunodeficiency virus(PLWH)and healthy individuals.Methods:Forty-seven PLWH and thirty healthy controls(HCs)inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study.The effect of SARS-CoV-2 vaccine on NK cell frequency,phenotype,and function in PLWH and HCs was evaluated by flow cytometry,and the response of NK cells to SARS-CoV-2 Omicron Spike(SARS-2-OS)protein stimulation was also evaluated.Results:SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH,which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine.However,in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers.Additionally,the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0,4 and 12 weeks,but the percentage of CD16^(+)NK cells in PLWH was significantly higher than that in HCs at 2,4 and 12 weeks after the third dose of vaccine.Interestingly,the frequency of CD16^(+)NK cells was significantly negatively correlated with the proportion of CD107a^(+)NK cells in PLWH at each time point after the third dose.Similarly,this phenomenon was also observed in HCs at 0,2,and 4 weeks after the third dose.Finally,regardless of whether NK cells were stimulated with SARS-2-OS or not,we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.Conclusions:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells,indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.
基金supported by grants from the National Key R&D Program of China(Nos.2021YFC2301900 and 2021YFC2301905)the National Natural Science Foundation of China(Nos.NSFC,81974303 and 82072271)+3 种基金Beijing Natural Science Foundation(Nos.L222068 and Z220018)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(Nos.2022-2-018 and 2022-1-007)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(Nos.DFL20191701)the Beijing Health Technologies Promotion Program(BHTPP202002)and Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089).
文摘Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(HIV)-infected individuals,ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs.To achieve a functional cure for HIV infection,numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART.Early studies have tested adoptive T-cell therapies in HIV-infected individuals,but their effectiveness was limited.In recent years,with the technological progress and great success of chimeric antigen receptor(CAR)therapy in the treatment of hematological malignancies,CAR therapy has gradually shown its advantages in the field of HIV infection.Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells.Therefore,CAR therapy may be beneficial for enhancing HIV immunity,achieving HIV control,and eliminating HIV reservoirs,gradually becoming a promising strategy for achieving a functional HIV cure.In this review,we provide an overview of the design of anti-HIV CAR proteins,the cell types of anti-HIV CAR(including CAR T cells,CAR natural killer cells,and CAR-encoding hematopoietic stem/progenitor cells),the clinical application of CAR therapy in HIV infection,and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.
基金supported by grants from the National Natural Science Foundation of China(NSFC,No.81974303)the National Key R&D Program of China(Nos.2021YFC2301900 and 2021YFC2301905)+2 种基金the Beijing Health Technologies Promotion Program(No.BHTPP202002)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(Nos.2022-2-018 and 2022-1-007)the Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089).
文摘To the Editor:Immune non-responders(INRs),who account for approximately 10-40%of human immunodeficiency virus(HIV)-infected individuals,have received effective treatment and exhibit persistent suppression of viral replication,but their CD4^(+)T-cell counts are not restored.They are likely to have an increased risk of non-acquired immunodeficiency syndrome(AIDS)-related morbidity and mortality compared with immune responders(IRs).[1]CD8^(+)T cells play an important role in viral infection,and the functional properties of circulating CD8^(+)T cells have been associated with immune control of HIV.High CD8^(+)T-cell counts are beneficial for persistent viral decay and CD4 T-cell recovery in immune-restored patients during long-term antiretroviral therapy(ART).[2]Two subsets of CD8^(+)T cells have been identified according to their intensity of CD8 expression:CD8^(bri)and CD8^(dim)T lymphocytes.It was demonstrated that CD3^(+)CD8^(dim)T cells,with weaker function than CD3^(+)CD8^(bri)T cells,were associated with disease progression during HIV infection.[3]However,dynamic changes in the numbers of CD8^(bri)and CD8^(dim)T cells in INRs and IRs before and after ART have not yet been reported.
基金R&D program of the Beijing Municipal Education Commission(No.KZ202210025037)Beijing Hospitals Authority Youth Program(No.QMS 20191202).
文摘Background:Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood-onset systemic lupus erythematosus (cSLE) are limited. Therefore, this study aimed to investigate circEPSTI1 expression in cSLE and evaluate its potential as a biomarker for diagnosing cSLE.Methods:This study included 70 children diagnosed with cSLE, 20 diagnosed with juvenile idiopathic arthritis (JIA), 20 diagnosed with juvenile dermatomyositis (JDM), and 50 healthy children at the Rheumatology Department of Beijing Children's Hospital from January 2019 to December 2019. Quantitative polymerase chain reaction was used to determine circEPSTI1 expression in the children. Correlations between circEPSTI1 and clinical features were assessed using Spearman's correlation test. Additionally, we calculated the receiver operating characteristic curve to assess the diagnostic efficacy.Results:We found that circEPSTI1 expression was higher in children with cSLE (4.62 ± 3.55) than that in healthy children (1.00 ± 0.45), those with JDM (1.06 ± 0.76), and those with JIA (0.96 ± 0.48). The area of the curve of circEPSTI1 was 0.892 (95% confidence interval [CI]: 0.832-0.952, p < 0.001) to discriminate children with SLE from healthy children, with a specificity of 0.814 and a sensitivity of 0.922. Children with lupus nephritis showed a higher circEPSTI1 expression than healthy children, those with JDM, and those with JIA. In addition, circEPSTI1 expression in children with SLE showed significant correlations with the SLE Disease Activity Index ( p < 0.0001) and C3 concentrations ( p = 0.001). Conclusion:Our study suggests that circEPSTI1 is a promising biomarker for the diagnosis and monitoring of cSLE.
基金supported by the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018 to B.S.)Beijing Key Laboratory for HIV/AIDS Research(BZ0089).The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency.The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system.Specifically,MPXV employs unique immune evasion strategies against a wide range of immunological elements,presenting a considerable challenge for treatment,especially following the discontinuation of routine smallpox vaccination among the general population.In this review,we start by discussing the entry of the mpox virus and the onset of early infection,followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses.Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection.With respect to adaptive immunity,mpox viruses exhibit unique and exceptional T-cell inhibition capabilities,thereby comprehensively remodeling the host immune environment.The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system.The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating.Finally,we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development.This review may provide valuable information for the development of new immunological treatments for mpox.
基金National Natural Science Foundation of China,Grant/Award Number:81701604R&D program of Beijing Municipal Education Commission,Grant/Award Number:202210025037。
文摘Importance:Systemic lupus erythematosus(SLE)is a diffuse connective tissue disease with complex clinical manifestations and prolonged course.The early diagnosis and condition monitoring of SLE are crucial to disease prognosis.Objective:To assess the diagnostic value of long noncoding RNA(lncRNA)nuclear enriched abundant transcript 1(NEAT1)in childhood-onset SLE(cSLE).Methods:Fifty-seven children diagnosed with SLE,40 children diagnosed with juvenile idiopathic arthritis(JIA),and 40 healthy children were included.Peripheral blood samples from each patient were collected.A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood.Associations among parameters were analyzed using the Mann-Whitney U test or independent sample t-test.Results:The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA.Receiver operating characteristic curves revealed an area under the curve(AUC)of 0.633(95%confidence interval[CI],0.524-0.742;P=0.024)for lncNEAT1_1.The AUC of lncNEAT1_2 was 0.812(95%CI,0.727-0.897;P<0.0001)to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925.Moreover,lncNEAT1_2 expression was higher in patients with cSLE presenting with fever,lupus nephritis,elevated erythrocyte sedimentation rate,active disease activity,and decreased C3 level,compared with those without these conditions.However,no similar correlation was observed for lncNEAT1_1.Interpretation:The expression of lncNEAT1_2 was significantly elevated in children with SLE,especially those with fever,renal involvement,and low C3 levels.These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.
