Dear Editor： Anti-sperm antibodies （ASAs） are composed of numerous antibodies interacting with multiple sperm antigens that play a role in fertility. In males, ASAs cause ＇immune infertility＇ by decreasing sperm ...Dear Editor： Anti-sperm antibodies （ASAs） are composed of numerous antibodies interacting with multiple sperm antigens that play a role in fertility. In males, ASAs cause ＇immune infertility＇ by decreasing sperm counts and normal forms, as well as reducing sperm motility and viability, markedly reducing the likelihood of natural conception. The development of ASA in the male depends on the release of sequestered antigens on germ cells following the disruption of the blood-testis barrier.展开更多
Under normal circumstances, spermatozoa are protected from the immune system by the blood-testis barrier. The breakdown of this barrier is the origin of the synthesis of antisperm antibodies (ASA). The presence of spe...Under normal circumstances, spermatozoa are protected from the immune system by the blood-testis barrier. The breakdown of this barrier is the origin of the synthesis of antisperm antibodies (ASA). The presence of sperm agglutinates in semen is characteristic of ASA. But is the presence of agglutinates in semen necessarily linked to the level of ASA in semen? The objective of this study was to assess the concentration of anti-sperm antibodies (ASA) in normozoosperms and infertile men with azoospermia. The biological material consisted of samples of human sperms: 30 samples with azoospermia and 32 with normozoospermia. The ASA assay was performed in seminal plasma using the DRG® Sperm Antibody ELISA (seminal plasma) kit (EIA-4249). The reading was carried out using a microplate reader at 450 nm. Data analysis was performed using Graph Pad Prism 7 software. The results obtained showed that the difference in ASA concentration between these two categories of sperm was not significant, with an average ASA level of 31.54 ± 2.45 U/mL in azoospermic ejaculate and 27.63 ± 1.51 U/mL in normozoosperms. Statistical analysis showed higher ASA concentrations in azoosperms with 6.67% of these declared positive. The ASA positivity rate made it possible to distinguish secretory azoospermias from obstructive ones. Also, the presence of ASA is not necessarily linked to the presence of agglutinates in the semen.展开更多
In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in ped...In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.展开更多
In medical research,there are times when the introduction of a new tool can launch scientific discovery in new directions.While antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)r...In medical research,there are times when the introduction of a new tool can launch scientific discovery in new directions.While antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic development.The recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).展开更多
In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care ...In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care floor and diagnosed with juvenile dermatomyositis and found to be positive for anti-Mi-2 alpha, anti-Mi-2 beta, and anti-MDA-5 antibodies. He gradually improved with a combination of steroid, immunomodulatory treatment, and physical therapy. This case outlines the clinical course of a patient with this rare disorder as well as the importance of understanding the role of associated antibodies to manage potential long-term sequelae.展开更多
The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated...The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated rejection(AMR)and the opportunities for improving transplant outcomes through better detection,prevention,and treatment strategies.As our understanding of the immunological mechanisms continues to evolve,so too will the approaches to managing and harnessing the power of antibodies in KT,ultimately leading to improved patient and graft survival.This narrative review explores the multifaceted roles of antibodies in KT,including their involvement in rejection mechanisms,advancements in desensitization protocols,AMR treatments,and their potential role in monitoring and improving graft survival.展开更多
Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin...Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.展开更多
Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, ...Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.展开更多
BACKGROUND At the end of December 2019,the world faced severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2),which led to the outbreak of coronavirus disease 2019(COVID-19),associated with respiratory issues.Thi...BACKGROUND At the end of December 2019,the world faced severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2),which led to the outbreak of coronavirus disease 2019(COVID-19),associated with respiratory issues.This virus has shown significant challenges,especially for senior citizens,patients with other underlying illnesses,or those with a sedentary lifestyle.Serological tests conducted early on have helped identify how the virus is transmitted and how to curb its spread.The study hypothesis was that the rapid serological test for SARS-CoV-2 antibodies could indicate the immunoreactive profile during the COVID-19 pandemic in a university population.AIM To conduct active surveillance for serological expression of anti-SARS-CoV-2 antibodies in individuals within a university setting during the COVID-19 pandemic.METHODS This sectional study by convenience sampling was conducted in a large university in Niteroi-RJ,Brazil,from March 2021 to July 2021.The study population consisted of students,faculty,and administrative staff employed by the university.A total of 3433 faculty members,60703 students,and 3812 administrative staff were invited to participate.Data were gathered through rapid serological tests to detect immunoglobulin(Ig)M and IgG against SARS-CoV-2.Theχ²or Fisher's exact test was used to conduct statistical analysis.A 0.20 significance level was adopted for variable selection in a multiple logistic regression model to evaluate associations.RESULTS A total of 1648 individuals were enrolled in the study.The proportion of COVID-19 positivity was 164/1648(9.8%).The adjusted logistic model indicate a positive association between the expression of IgM or IgG and age[odds ratio(OR)=1.16,95%CI:1.02-1.31](P<0.0024),individuals who had been in contact with a COVID-19-positive case(OR=3.49,95%CI:2.34-5.37)(P<0.001),those who had received the COVID-19 vaccine(OR=2.33,95%CI:1.61-3.35)(P<0.001)and social isolation(OR=0.59,95%CI:0.41-0.84)(P<0.004).The likelihood of showing a positive result increased by 16%with every ten-year increment.Conversely,adherence to social distancing measures decreased the likelihood by 41%.CONCLUSION These findings evidenced that the population became more exposed to the virus as individuals discontinued social distancing practices,thereby increasing the risk of infection for themselves.展开更多
HLA-C,HLA-DP and HLA-DQ are thought to be benign due to low expression and few initial negative studies.Historically,most allocation programs used HLA-A,HLA-B and HLA-DR antigens for matching.With the advent and use o...HLA-C,HLA-DP and HLA-DQ are thought to be benign due to low expression and few initial negative studies.Historically,most allocation programs used HLA-A,HLA-B and HLA-DR antigens for matching.With the advent and use of single-bead antigen assays,more was learned about donor-specific antibodies(DSAs)against these antigens.Interest in these antigens and antibodies grew when cases of acute antibody-mediated rejection(AMR),mixed rejections,chronic AMR,and reduced graft survival were reported with DSAs against these antigens.Although the deleterious effects of these DSAs are more pronounced in retransplants,harmful effects have also been observed in first-time recipients.DSAs against each of these antigens can trigger rejection alone.Their combination with DSAs against HLA-A,HLA-B and HLA-DR can cause more damage.It has been shown that strategies that reduce mismatches for these antigen lead to fewer rejections and better graft survival.There is a need for greater consensus on the universal typing of these antigens prior to transplantation for better patient and graft outcomes.This review focuses on the interaction of these antigens with lymphocytes and killer immunoglobulin receptors,arguments for not typing them,detailed analyses of the literature about their harmful effects,potential strategies moving forward,and recommendations for the future.展开更多
BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impa...BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impaired cognitive function,behavioral and psychological disorders,and seizures.Paraneoplastic LE can occur when an immune response is activated due to antibodies targeting gammaaminobutyric acid(GABA)B receptor(GABABR)interacting with antigens on tumor cells and the nervous system,resulting in tumors primarily as small cell lung carcinoma(SCLC).CASE SUMMARY We discuss two cases of GABABR antibody-related LE resulting from SCLC.The patients’symptoms were managed with immunotherapy but ended in premature death due to chemotherapy-related complications.CONCLUSION Paraneoplastic syndrome is a notable cause of LE.Early intravenous immunoglobulin therapy may lead to temporary remission.展开更多
Antibodies as therapeutic agents are mostly used in oncology, as illustrated by their applications in lymphoma, breast cancer or colorectal cancer. This review provides a brief historical sketch of the development of ...Antibodies as therapeutic agents are mostly used in oncology, as illustrated by their applications in lymphoma, breast cancer or colorectal cancer. This review provides a brief historical sketch of the development of monoclonal antibodies for cancer treatment and summarizes the most significant clinical data for the best-established reagents to date. It also discusses strategies to improve the anti-tumor efficacy of antibody therapy, including antibody gene therapy and exploitation of bone marrow derived primary mesenchymal stem cells as the antibody gene transporter.展开更多
Testis-specific protease 50 （TSP50） is a testis-specific oncogene, which is abnormally activated in most tested patients with breast cancer. This property makes it an attractive molecular marker and a promising targ...Testis-specific protease 50 （TSP50） is a testis-specific oncogene, which is abnormally activated in most tested patients with breast cancer. This property makes it an attractive molecular marker and a promising target for the diagnosis and therapy of breast cancer. In order to obtain the protective and specific polyclonal antibodies for further research, TSPS0 cDNA was amplified by RT-PCR from normal human testicular tissue, and inserted into eukaryotic expression vector PeDNA3.1. Rabbit anti-TSPS0 polyclonal antibodies were prepared by means of intramuscular injection of peDNA3.1-TSPS0 into the rabbits. Titem of the anti-sera were measured by ELISA and Western blotting with the E. coli cell lysate containing the induced GST-TSPS0 fusion protein as an antigen. In addition, we examined the expression of TSPS0 in both breast cancer cell line MCF-7 and breast cancer tissue by immunofluorescent and immunohistochemistry analysis.展开更多
A monoclonal antibody was first prepared by fusion of mouse myeloma cells (SP2/0-Ag-14) with spleen cells isolated from male BALB/ c mice immunized with spermidine-bovine serum albumin conjugate (SPD- BSA). The hybrid...A monoclonal antibody was first prepared by fusion of mouse myeloma cells (SP2/0-Ag-14) with spleen cells isolated from male BALB/ c mice immunized with spermidine-bovine serum albumin conjugate (SPD- BSA). The hybridoma cell line producing antibody specific for spermidine was cultured in vitro and after i. p. into mice, the ascitic fluid gave suitably high dilution titres (1: 106) by enzyme immunoassay. This monoclonal antibody is of IgG1 class and the bimolecular compleex with molecular weight of 52KD and 27 KD. The monoclonal antibody was clearly specific to spermidine comparing with spermine or putriscine. Monclonal antibody may prove to be useful in the rapid diagnosis and evaluation of patients with cancer.展开更多
Objective: To isolate murine anti endotoxin single chain phage antibody from a constructed library. Methods: Total RNA was firstly extracted from murine splenic cells and mRNA was reverse-transcribed into cDNA. Then t...Objective: To isolate murine anti endotoxin single chain phage antibody from a constructed library. Methods: Total RNA was firstly extracted from murine splenic cells and mRNA was reverse-transcribed into cDNA. Then the designed primers were used to amplify the variable region genes of the heavy and light chain (VH, VL) with polymerase chain reaction. The linker was used to assemble the VH and VL into ScFv, and the NotI and SfiI restriction enzymes were used to digest the ScFv in order to ligate into the pCANTAB5E phagemid vector that was already digested with the same restriction enzymes. The ligated vector was then introduced into competent E.coli TG1 cells to construct a single-chain phage antibody library. After rescued with M13KO7 helper phage, recombinant phages displaying ScFv fragments were harvested from the supernatant and selected with endotoxin. The enriched positive clones were reinfected into TG1 cells. Finally, 190 clones were randomly selected to detect the anti endotoxin antibody with indirect ELISA. Results: The titer of anti endotoxin in murine sera was 1:12,800. The concentration of total RNA was 12.38 μg/ml. 1.9×107 clones were obtained after transformed into TG1. 3×104 colonies were gotten after one round panning. Two positive colonies were confirmed with indirect ELISA among 190 randomly selected colonies. Conclusion: A 1.9×107 murine anti endotoxin single chain phage antibody library was successfully constructed. Two anti endotoxin antibodies were obtained from the library.展开更多
Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside a...Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.展开更多
The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice t...The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice （6–8 weeks old） were randomized into 3 groups： dilated cardiomyopathy （DCM） group, DCM-tolerance （Tol） group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group （P〈0.01）. On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group （P〈0.01）, and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.展开更多
Introduction: Infertility in a couple is a stressful situation. Among the causes is the presence of antisperm antibodies that play a harmful role in reducing fertility and negatively influencing in vitro fertilization...Introduction: Infertility in a couple is a stressful situation. Among the causes is the presence of antisperm antibodies that play a harmful role in reducing fertility and negatively influencing in vitro fertilization. The aim of this study is to determine their prevalence among infertile patients in Kisangani. Patients and methods: We conducted an analytical cross-sectional study in health facilities in the city of Kisangani. Of the 1379 patients who consulted for conception, 311 were tested for antisperm antibodies by ELISA. Results: Of the 311 patients, 121 tested positive (38.91%). Women were significantly more likely to be positive (p-value = 0.013). Ig G was positive in 32.48% of patients and Ig A in 10.93%. Age was a significant predictor of the number of positive patients (p-value < 0.001). Compared to patients of ≤30 years of age, having 31 to 40 years of age or 41 years of age and older increased respectively 2 and 3 times the risk of being positive. In secondary infertility, women are twice as likely to be positive. Conclusion: The prevalence of antisperm antibodies is very high among infertile patients in Kisangani with predominance among women. Older age increases the risk of positivity. This test should therefore be integrated into infertility investigations as often as possible.展开更多
BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft...BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft longevity.While substantial evidence for adult populations exists,research focusing on pediatric LT outcomes remains limited.AIM To investigate the prevalence of human leukocyte antigen(HLA)mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.METHODS A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre,Brazil,between December 2013 and December 2023.Only patients who survived for>30 days after LT with at least one DSA analysis were included.DSA classes I and II and cross-matches were analyzed.The presence of de novo DSA(dnDSA)was evaluated at least 3 months after LT using the Luminex®single antigen bead method,with a positive reaction threshold set at 1000 MFI.Rejection episodes were confirmed by liver biopsy.RESULTS Overall,67 transplanted children were analyzed;61 received grafts from living donors,85%of whom were related to recipients.Pre-transplant DSA(class I or II)was detected in 28.3%of patients,and dnDSA was detected in 48.4%.The median time to DSA detection after LT was 19.7[interquartile range(IQR):4.3-35.6]months.Biopsyproven rejection occurred in 13 patients at follow-up,with C4d positivity observed in 5/13 Liver biopsies.The median time to rejection was 7.8(IQR:5.7-12.8)months.The presence of dnDSA was significantly associated with rejection(36%vs 3%,P<0.001).The rejection-free survival rates at 12 and 24 months were 76%vs 100%and 58%vs 95%for patients with dnDSA anti-DQ vs those without,respectively.CONCLUSION Our findings highlight the importance of incorporating DSA assessment into pre-and post-transplantation protocols for pediatric LT recipients.Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.展开更多
Introduction: Antisperm antibodies (ASA) prevalence is high in Kisangani. ASA are one of the male factors of infertility that can reduce spermatozoa motility and cervical penetration or prevent acrosomal reaction and ...Introduction: Antisperm antibodies (ASA) prevalence is high in Kisangani. ASA are one of the male factors of infertility that can reduce spermatozoa motility and cervical penetration or prevent acrosomal reaction and even alter embryo development. This study aims to determine the risk factors of ASA positivity among infertile men in Kisangani. Patient and Method: We conducted a case-control study during a period of 2 years in Kisangani on 111 men who consulted for conception and tested for ASA by ELISA. We did a simple pairing that concerned only the type of infertility. For a better balance between the number of cases and controls per stratum to provide better accuracy in the adjusted OR estimate, we performed a 1:1 match. Results: This study showed that businessmen [ORa = 5.0000(1.2452 - 20.0767)] and jobless [ORa = 5.8125(1.1477 - 29.4367)] were at risk of being positive for ASA. Violent blow to testicles [ORa = 6.7391(1.3455 - 33.7545)], cure of hernia [ORa = 4.3478(1.0722 - 17.6299)], Chlamydia infection [ORa = 4.7125(1.3405 - 16.5665)], leucospermia [ORa = 4.1429(1.0406 - 19.7155)] and presence of Staphylococcus aureus [ORa = 3.4444(0.6410 - 18.5082)] were associated to positive ASA. Conclusion: This study shows that factors that may lead to risky sexual behavior and physical or infectious trauma are important risk factors for ASA positivity. It is therefore necessary to search for them systematically during male infertility in order to guide the search for ASA.展开更多
文摘Dear Editor： Anti-sperm antibodies （ASAs） are composed of numerous antibodies interacting with multiple sperm antigens that play a role in fertility. In males, ASAs cause ＇immune infertility＇ by decreasing sperm counts and normal forms, as well as reducing sperm motility and viability, markedly reducing the likelihood of natural conception. The development of ASA in the male depends on the release of sequestered antigens on germ cells following the disruption of the blood-testis barrier.
文摘Under normal circumstances, spermatozoa are protected from the immune system by the blood-testis barrier. The breakdown of this barrier is the origin of the synthesis of antisperm antibodies (ASA). The presence of sperm agglutinates in semen is characteristic of ASA. But is the presence of agglutinates in semen necessarily linked to the level of ASA in semen? The objective of this study was to assess the concentration of anti-sperm antibodies (ASA) in normozoosperms and infertile men with azoospermia. The biological material consisted of samples of human sperms: 30 samples with azoospermia and 32 with normozoospermia. The ASA assay was performed in seminal plasma using the DRG® Sperm Antibody ELISA (seminal plasma) kit (EIA-4249). The reading was carried out using a microplate reader at 450 nm. Data analysis was performed using Graph Pad Prism 7 software. The results obtained showed that the difference in ASA concentration between these two categories of sperm was not significant, with an average ASA level of 31.54 ± 2.45 U/mL in azoospermic ejaculate and 27.63 ± 1.51 U/mL in normozoosperms. Statistical analysis showed higher ASA concentrations in azoosperms with 6.67% of these declared positive. The ASA positivity rate made it possible to distinguish secretory azoospermias from obstructive ones. Also, the presence of ASA is not necessarily linked to the presence of agglutinates in the semen.
文摘In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.
文摘In medical research,there are times when the introduction of a new tool can launch scientific discovery in new directions.While antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic development.The recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).
文摘In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care floor and diagnosed with juvenile dermatomyositis and found to be positive for anti-Mi-2 alpha, anti-Mi-2 beta, and anti-MDA-5 antibodies. He gradually improved with a combination of steroid, immunomodulatory treatment, and physical therapy. This case outlines the clinical course of a patient with this rare disorder as well as the importance of understanding the role of associated antibodies to manage potential long-term sequelae.
文摘The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated rejection(AMR)and the opportunities for improving transplant outcomes through better detection,prevention,and treatment strategies.As our understanding of the immunological mechanisms continues to evolve,so too will the approaches to managing and harnessing the power of antibodies in KT,ultimately leading to improved patient and graft survival.This narrative review explores the multifaceted roles of antibodies in KT,including their involvement in rejection mechanisms,advancements in desensitization protocols,AMR treatments,and their potential role in monitoring and improving graft survival.
文摘Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.
文摘Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.
文摘BACKGROUND At the end of December 2019,the world faced severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2),which led to the outbreak of coronavirus disease 2019(COVID-19),associated with respiratory issues.This virus has shown significant challenges,especially for senior citizens,patients with other underlying illnesses,or those with a sedentary lifestyle.Serological tests conducted early on have helped identify how the virus is transmitted and how to curb its spread.The study hypothesis was that the rapid serological test for SARS-CoV-2 antibodies could indicate the immunoreactive profile during the COVID-19 pandemic in a university population.AIM To conduct active surveillance for serological expression of anti-SARS-CoV-2 antibodies in individuals within a university setting during the COVID-19 pandemic.METHODS This sectional study by convenience sampling was conducted in a large university in Niteroi-RJ,Brazil,from March 2021 to July 2021.The study population consisted of students,faculty,and administrative staff employed by the university.A total of 3433 faculty members,60703 students,and 3812 administrative staff were invited to participate.Data were gathered through rapid serological tests to detect immunoglobulin(Ig)M and IgG against SARS-CoV-2.Theχ²or Fisher's exact test was used to conduct statistical analysis.A 0.20 significance level was adopted for variable selection in a multiple logistic regression model to evaluate associations.RESULTS A total of 1648 individuals were enrolled in the study.The proportion of COVID-19 positivity was 164/1648(9.8%).The adjusted logistic model indicate a positive association between the expression of IgM or IgG and age[odds ratio(OR)=1.16,95%CI:1.02-1.31](P<0.0024),individuals who had been in contact with a COVID-19-positive case(OR=3.49,95%CI:2.34-5.37)(P<0.001),those who had received the COVID-19 vaccine(OR=2.33,95%CI:1.61-3.35)(P<0.001)and social isolation(OR=0.59,95%CI:0.41-0.84)(P<0.004).The likelihood of showing a positive result increased by 16%with every ten-year increment.Conversely,adherence to social distancing measures decreased the likelihood by 41%.CONCLUSION These findings evidenced that the population became more exposed to the virus as individuals discontinued social distancing practices,thereby increasing the risk of infection for themselves.
文摘HLA-C,HLA-DP and HLA-DQ are thought to be benign due to low expression and few initial negative studies.Historically,most allocation programs used HLA-A,HLA-B and HLA-DR antigens for matching.With the advent and use of single-bead antigen assays,more was learned about donor-specific antibodies(DSAs)against these antigens.Interest in these antigens and antibodies grew when cases of acute antibody-mediated rejection(AMR),mixed rejections,chronic AMR,and reduced graft survival were reported with DSAs against these antigens.Although the deleterious effects of these DSAs are more pronounced in retransplants,harmful effects have also been observed in first-time recipients.DSAs against each of these antigens can trigger rejection alone.Their combination with DSAs against HLA-A,HLA-B and HLA-DR can cause more damage.It has been shown that strategies that reduce mismatches for these antigen lead to fewer rejections and better graft survival.There is a need for greater consensus on the universal typing of these antigens prior to transplantation for better patient and graft outcomes.This review focuses on the interaction of these antigens with lymphocytes and killer immunoglobulin receptors,arguments for not typing them,detailed analyses of the literature about their harmful effects,potential strategies moving forward,and recommendations for the future.
文摘BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impaired cognitive function,behavioral and psychological disorders,and seizures.Paraneoplastic LE can occur when an immune response is activated due to antibodies targeting gammaaminobutyric acid(GABA)B receptor(GABABR)interacting with antigens on tumor cells and the nervous system,resulting in tumors primarily as small cell lung carcinoma(SCLC).CASE SUMMARY We discuss two cases of GABABR antibody-related LE resulting from SCLC.The patients’symptoms were managed with immunotherapy but ended in premature death due to chemotherapy-related complications.CONCLUSION Paraneoplastic syndrome is a notable cause of LE.Early intravenous immunoglobulin therapy may lead to temporary remission.
文摘Antibodies as therapeutic agents are mostly used in oncology, as illustrated by their applications in lymphoma, breast cancer or colorectal cancer. This review provides a brief historical sketch of the development of monoclonal antibodies for cancer treatment and summarizes the most significant clinical data for the best-established reagents to date. It also discusses strategies to improve the anti-tumor efficacy of antibody therapy, including antibody gene therapy and exploitation of bone marrow derived primary mesenchymal stem cells as the antibody gene transporter.
文摘Testis-specific protease 50 （TSP50） is a testis-specific oncogene, which is abnormally activated in most tested patients with breast cancer. This property makes it an attractive molecular marker and a promising target for the diagnosis and therapy of breast cancer. In order to obtain the protective and specific polyclonal antibodies for further research, TSPS0 cDNA was amplified by RT-PCR from normal human testicular tissue, and inserted into eukaryotic expression vector PeDNA3.1. Rabbit anti-TSPS0 polyclonal antibodies were prepared by means of intramuscular injection of peDNA3.1-TSPS0 into the rabbits. Titem of the anti-sera were measured by ELISA and Western blotting with the E. coli cell lysate containing the induced GST-TSPS0 fusion protein as an antigen. In addition, we examined the expression of TSPS0 in both breast cancer cell line MCF-7 and breast cancer tissue by immunofluorescent and immunohistochemistry analysis.
文摘A monoclonal antibody was first prepared by fusion of mouse myeloma cells (SP2/0-Ag-14) with spleen cells isolated from male BALB/ c mice immunized with spermidine-bovine serum albumin conjugate (SPD- BSA). The hybridoma cell line producing antibody specific for spermidine was cultured in vitro and after i. p. into mice, the ascitic fluid gave suitably high dilution titres (1: 106) by enzyme immunoassay. This monoclonal antibody is of IgG1 class and the bimolecular compleex with molecular weight of 52KD and 27 KD. The monoclonal antibody was clearly specific to spermidine comparing with spermine or putriscine. Monclonal antibody may prove to be useful in the rapid diagnosis and evaluation of patients with cancer.
基金This work was supported by the National Natural Science Foundation (No. 39570042).
文摘Objective: To isolate murine anti endotoxin single chain phage antibody from a constructed library. Methods: Total RNA was firstly extracted from murine splenic cells and mRNA was reverse-transcribed into cDNA. Then the designed primers were used to amplify the variable region genes of the heavy and light chain (VH, VL) with polymerase chain reaction. The linker was used to assemble the VH and VL into ScFv, and the NotI and SfiI restriction enzymes were used to digest the ScFv in order to ligate into the pCANTAB5E phagemid vector that was already digested with the same restriction enzymes. The ligated vector was then introduced into competent E.coli TG1 cells to construct a single-chain phage antibody library. After rescued with M13KO7 helper phage, recombinant phages displaying ScFv fragments were harvested from the supernatant and selected with endotoxin. The enriched positive clones were reinfected into TG1 cells. Finally, 190 clones were randomly selected to detect the anti endotoxin antibody with indirect ELISA. Results: The titer of anti endotoxin in murine sera was 1:12,800. The concentration of total RNA was 12.38 μg/ml. 1.9×107 clones were obtained after transformed into TG1. 3×104 colonies were gotten after one round panning. Two positive colonies were confirmed with indirect ELISA among 190 randomly selected colonies. Conclusion: A 1.9×107 murine anti endotoxin single chain phage antibody library was successfully constructed. Two anti endotoxin antibodies were obtained from the library.
基金supported by Fondo para la Investigación Cientifica y Tecnológica(FONCy T),Argentina,grant#PICT 2015-2473(to PHHL)supported by grants from National Institute of Health/National Institute of Neurological Disorders and Stroke(NIH/NINDS,USA)(NS121621)+2 种基金Department of Defense,USA(Do D-CL1)(PR200530)partially financed with a fellowship for Research in Medicine from Fundación Florencio Fiorinisupported with a PhD fellowship from CONICET。
文摘Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.
基金the National Natural Science Foundation of China (No. 30000070)
文摘The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice （6–8 weeks old） were randomized into 3 groups： dilated cardiomyopathy （DCM） group, DCM-tolerance （Tol） group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group （P〈0.01）. On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group （P〈0.01）, and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.
文摘Introduction: Infertility in a couple is a stressful situation. Among the causes is the presence of antisperm antibodies that play a harmful role in reducing fertility and negatively influencing in vitro fertilization. The aim of this study is to determine their prevalence among infertile patients in Kisangani. Patients and methods: We conducted an analytical cross-sectional study in health facilities in the city of Kisangani. Of the 1379 patients who consulted for conception, 311 were tested for antisperm antibodies by ELISA. Results: Of the 311 patients, 121 tested positive (38.91%). Women were significantly more likely to be positive (p-value = 0.013). Ig G was positive in 32.48% of patients and Ig A in 10.93%. Age was a significant predictor of the number of positive patients (p-value < 0.001). Compared to patients of ≤30 years of age, having 31 to 40 years of age or 41 years of age and older increased respectively 2 and 3 times the risk of being positive. In secondary infertility, women are twice as likely to be positive. Conclusion: The prevalence of antisperm antibodies is very high among infertile patients in Kisangani with predominance among women. Older age increases the risk of positivity. This test should therefore be integrated into infertility investigations as often as possible.
基金approved by the Ethics and Research Committee of the Federal University of Health Sciences of Porto Alegre(UFCSPA)and the Santa Casa de Misericórdia de Porto Alegre Complex(ISCMPA)(approval numbers 3805918 and 3938979,respectively)the Brazilian Clinical Trials Registry(ReBec)under number RBR-3 gtcvjU111112367585.
文摘BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft longevity.While substantial evidence for adult populations exists,research focusing on pediatric LT outcomes remains limited.AIM To investigate the prevalence of human leukocyte antigen(HLA)mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.METHODS A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre,Brazil,between December 2013 and December 2023.Only patients who survived for>30 days after LT with at least one DSA analysis were included.DSA classes I and II and cross-matches were analyzed.The presence of de novo DSA(dnDSA)was evaluated at least 3 months after LT using the Luminex®single antigen bead method,with a positive reaction threshold set at 1000 MFI.Rejection episodes were confirmed by liver biopsy.RESULTS Overall,67 transplanted children were analyzed;61 received grafts from living donors,85%of whom were related to recipients.Pre-transplant DSA(class I or II)was detected in 28.3%of patients,and dnDSA was detected in 48.4%.The median time to DSA detection after LT was 19.7[interquartile range(IQR):4.3-35.6]months.Biopsyproven rejection occurred in 13 patients at follow-up,with C4d positivity observed in 5/13 Liver biopsies.The median time to rejection was 7.8(IQR:5.7-12.8)months.The presence of dnDSA was significantly associated with rejection(36%vs 3%,P<0.001).The rejection-free survival rates at 12 and 24 months were 76%vs 100%and 58%vs 95%for patients with dnDSA anti-DQ vs those without,respectively.CONCLUSION Our findings highlight the importance of incorporating DSA assessment into pre-and post-transplantation protocols for pediatric LT recipients.Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.
文摘Introduction: Antisperm antibodies (ASA) prevalence is high in Kisangani. ASA are one of the male factors of infertility that can reduce spermatozoa motility and cervical penetration or prevent acrosomal reaction and even alter embryo development. This study aims to determine the risk factors of ASA positivity among infertile men in Kisangani. Patient and Method: We conducted a case-control study during a period of 2 years in Kisangani on 111 men who consulted for conception and tested for ASA by ELISA. We did a simple pairing that concerned only the type of infertility. For a better balance between the number of cases and controls per stratum to provide better accuracy in the adjusted OR estimate, we performed a 1:1 match. Results: This study showed that businessmen [ORa = 5.0000(1.2452 - 20.0767)] and jobless [ORa = 5.8125(1.1477 - 29.4367)] were at risk of being positive for ASA. Violent blow to testicles [ORa = 6.7391(1.3455 - 33.7545)], cure of hernia [ORa = 4.3478(1.0722 - 17.6299)], Chlamydia infection [ORa = 4.7125(1.3405 - 16.5665)], leucospermia [ORa = 4.1429(1.0406 - 19.7155)] and presence of Staphylococcus aureus [ORa = 3.4444(0.6410 - 18.5082)] were associated to positive ASA. Conclusion: This study shows that factors that may lead to risky sexual behavior and physical or infectious trauma are important risk factors for ASA positivity. It is therefore necessary to search for them systematically during male infertility in order to guide the search for ASA.
