Targeted treatment of cancer with monoclonal antibodies increases the benefit for patients. In order to improve the anti-tumor activity of monoclonal antibodies, multi-specific antibodies have entered the research fie...Targeted treatment of cancer with monoclonal antibodies increases the benefit for patients. In order to improve the anti-tumor activity of monoclonal antibodies, multi-specific antibodies have entered the research field. The emergence of various techniques to produce multi-specific recombinant antibody molecules has led to the selection of target combinations in various forms. To date, only a few multi-specific constructs have entered phase III clinical trials, in contrast to classical monoclonal antibodies. Some of the format options are outlined from a technical point of view. We focus on the achievements and prospects of the underlying technologies for generating biand multispecific antibodies.展开更多
Porcine deltacoronavirus(PDCoV)is an emerging swine enteropathogenic coronavirus that can cause acute diarrhea and vomiting in newborn piglets and poses a potential risk for cross-species transmission.It is necessary ...Porcine deltacoronavirus(PDCoV)is an emerging swine enteropathogenic coronavirus that can cause acute diarrhea and vomiting in newborn piglets and poses a potential risk for cross-species transmission.It is necessary to develop an effective serological diagnostic tool for the surveillance of PDCoV infection and vaccine immunity effects.In this study,we developed a monoclonal antibody-based competitive ELISA(cELISA)that selected the purified recombinant PDCoV nucleocapsid(N)protein as the coating antigen to detect PDCoV antibodies.To evaluate the diagnostic performance of the cELISA,122 swine serum samples(39 positive and 83 negative)were tested and the results were compared with an indirect immunofluorescence assay(IFA)as the reference method.By receiver operating characteristic(ROC)curve analysis,the optimum cutoff value of percent inhibition(PI)was determined to be 26.8%,which showed excellent diagnostic performance,with an area under the curve(AUC)of 0.9919,a diagnostic sensitivity of 97.44%and a diagnostic specificity of 96.34%.Furthermore,there was good agreement between the cELISA and virus neutralization test(VNT)for the detection of PDCoV antibodies,with a coincidence rate of 92.7%,and theκanalysis showed almost perfect agreement(κ=0.851).Overall,the established cELISA showed good diagnostic performance,including sensitivity,specificity and repeatability,and can be used for diagnostic assistance,evaluating the response to vaccination and assessing swine herd immunity.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
As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lu...As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lung cancer treatment,a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance.Bispecific antibodies(bs Abs)bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles,thus attracting increasing attention as novel antitumor therapies.At present,in addition to the approved bs Ab,amivantamab,three novel bs Abs(KN046,AK112,and SHR-1701)are being evaluated in phase 3 clinical trials and many bs Abs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer(NSCLC).Herein we present the structure,classification,and mechanism of action underlying bs Abs in NSCLC and introduce related clinical trials.Finally,we discuss challenges,potential solutions,and future prospects in the context of cancer treatment with bsAbs.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
[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the...[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the potential of polyclonal yolk antibodies(IgY)harvested from laying hens immunized with the rMKIBV vaccine in the prevention and control of IBV.[Methods]The antigenic epitope sequences of IBV,obtained from online databases,were compared with sequences of representative IBV strains from GenBank.Flexible peptides were designed to link all antigenic peptides.The constructed amino acid sequence was analyzed,reverse-translated,codon-optimized,and then inserted into the pET-28a(+)cloning vector.The recombinant vector was introduced into Escherichia coli for expression.The purified,desalted,and endotoxin-removed rMKIBV protein was used as a vaccine to immunize animals for investigation of its immunogenicity and ability to stimulate specific IgY production in laying hens.[Results]The retrieved IBV antigenic epitope sequences showed high similarity with the published N and S protein sequences of 22 representative IBV strains.The predicted isoelectric point and molecular weight of rMKIBV were 10.25 and 63.39 kDa,respectively.The secondary structure of rMKIBV included a high proportion of random coils,which suggested strong antigenicity.High-purity rMKIBV was obtained from E.coli transformed with the recombinant plasmid pET-28a-mkibv.This protein specifically bound to anti-His-tag antibodies,N protein antibodies,and S protein antibodies.The mice immunized with this protein showed increases in the spleen index(P<0.05),elevations in the levels of serum-specific IgG antibodies(P<0.01)and IFN-γ(P<0.05),and no significant change in the IL-2 level.Immunized laying hens successfully produced IgY in egg yolks,with specific IgY antibody levels significantly increasing.Moreover,the IgY antibody titer gradually rose after immunization,reaching the peak after about 50 days and then gradually declining to reach a stable level.[Conclusion]We successfully constructed and expressed the recombinant protein rMKIBV.The protein demonstrated good immunogenicity,stimulating specific antibody production in both mice and laying hens.Notably,the IgY extracted from the yolks of immunized laying hens offers a novel approach to IBV prevention and control.These findings hold significant scientific and practical value for the development of vaccines against IBV.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 This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with A...BACKGROUND This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with Avacopan.Although relapsing polychondritis has been associated with anti-neutrophil cytoplasmic antibody-associated vasculitis,overlap can result in severe organ involvement,particularly renal damage progressing to end-stage kidney disease.This case presents a unique opportunity to evaluate the potential role of Avacopan as an alternative therapeutic option in managing myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated vasculitis in the context of relapsing polychon-dritis highlighting a positive renal response despite treatment challenges.This is a case of a 69-year-old Caucasian woman who presented to our hospital’s emergency department with a 4 week history of inflammatory polychondritis affecting the auricular cartilage,accompanied by acute kidney injury.On admission,serum creatinine was elevated at 4.0 mg/dL,which progressively increased to 6.07 mg/dL on day 6.The renal biopsy revealed necrotizing and crescentic glomerulonephritis affecting more than 50%of the glomeruli.She was treated with a total of 2500 mg intravenous methylprednisolone over 3 days followed by oral prednisone.Induction treatment included intravenous cyclophosphamide induction,with plans for a total of 2 doses followed by transition to rituximab.However the patient was unable to tolerate rituximab due to allergic reaction so intravenous cyclophosphamide was continued for a total of 6 doses(cumulative dose 3000 mg).In the setting of persistent acute kidney injury,Avacopan was added to the regimen 3 months after diagnosis.Maintenance therapy included azathioprine in addition to Avacopan.Prednisone gradually tapered off at 6 months.CONCLUSION Avacopan may be beneficial in treating anti-neutrophil cytoplasmic antibody-associated vasculitis with coexisting relapsing polychondritis,especially in cases where preservation of kidney function is critical.Further research will be essential to validate these findings and refine treatment protocols for such complex cases.展开更多
BACKGROUND Patients with inflammatory bowel diseases(IBD)often miss the scheduled vaccines and have a higher risk of infection susceptibility,including vaccineprevented diseases.AIM To evaluate the vaccine coverage an...BACKGROUND Patients with inflammatory bowel diseases(IBD)often miss the scheduled vaccines and have a higher risk of infection susceptibility,including vaccineprevented diseases.AIM To evaluate the vaccine coverage and levels of the post-vaccine antibodies against measles,mumps,rubella,and hepatitis B in children with IBD.METHODS Total 98 patients:46 females(47.2%)and 52 males(52.8%)with IBD(Crohn’s disease-75%and ulcerative colitis-25%)with disease onset age-11.0(6.0;14.0)years whom clinical data,vaccination status and levels of the postvaccination antibodies(IgG)for measles,rubella,mumps,hepatitis B,measured with ELISA were prospectively evaluated.The control group consisted of 88 healthy peers from the biobank data.RESULTS Patients with IBD had lower levels of measles,rubella,and hepatitis B,except mumps,compared to controls.Incomplete vaccination/non-protective titer of the antibodies against measles,mumps rubella,and hepatitis B had 33(33.7%)/52.3%,21(21.4%)/50.4%,26(25.8)/25.6%and 26(25.8%)/55.2%,respectively.Patients with incomplete vaccination had a lower age at the diagnosis for all vaccines.The age of the IBD diagnosis≤6 years was the predictor of incomplete vaccination for measles[odds ratio(OR)=4.6,P=0.001],mumps(OR=5.0,P=0.001),rubella(OR=5.4,P=0.0005)and hepatitis B(OR=5.4,P=0.0005)and corticosteroid treatment for measles(OR=2.2,P=0.074)and mumps(OR=3.0,P=0.047)vaccines.Incomplete vaccination was the predictor of nonprotective titer of antibodies against rubella(OR=6.8,95%CI:2.3-19.9,P=0.0002)/mumps(OR=7.0,95%CI:2.4-20.8;P=0.0002).CONCLUSION Patients with IBD had low vaccine coverage and lower levels of anti-vaccine antibodies against measles,rubella,and hepatitis B.Nearly half of the IBD patients require revaccination.展开更多
The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspe...The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research.Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials,which were selected between 2022 and 2023,in order to understand better the monoclonal antibodies that were most studied.The biopharmaceutical compounds Ibrutinib,Obinutuzumab,Rituximab,Venetoclax,and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications,indicating the importance of amplifying the studies.The action mechanisms that are used imply that their combined use has more success in the disease remission,showing a lower recurrence,adverse effects,and toxicity.Besides the adverse effects and overwhelming prices of the treatment,these immunotherapies results are promising,amplifying the survival rates,improving the patient’s life quality,and resulting in a precision medicine,aiming a custom treatment.The future perspectives on this therapy consist of its application in the public health system,with patients being able to be submitted to this treatment without any costs and receive a better life quality.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
Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst m...Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst min-imising off-target effects.This review provides a comprehensive analysis of ADCs,encompassing their structural components,mechanisms of action,and clinical applications.It also examines recent technological advancements,particularly in antibody engineering and linker design,aimed at enhancing therapeutic efficacy and safety.The current clinical landscape is outlined,highlighting approved ADCs and promising candidates in clinical trials,while also addressing key challenges such as stability,half-life,and systemic toxicity.This review is based on an extensive literature survey from major databases such as Scopus and Web of Science,with a focus on keywords like“antibody-drug conjugates”,“ADC advancements”,and“next-generation ADC technologies”.By integrating insights from both preclinical and clinical perspectives,we highlight the transformative potential of ADCs in advancing modern cancer therapy.展开更多
Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safet...Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics.展开更多
Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which...Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which recognize and bind to specific target antigens present within the transplanted kidney tissue.Upon binding,these DSAs commonly initiate activation of the complement system within the graft.The activation of the complement cascade sets off a powerful inflammatory response characterized by the recruitment and activation of immune cells,endothelial damage,and subsequent tissue injury.This inflammation underlies many clinical and histological manifestations of AMR,making complement activation a critical player in the disease process.Advancements in our understanding of how complement pathways contribute to kidney graft injury have opened new avenues for therapeutic intervention.Recent research has facilitated the development and application of novel therapies specifically designed to inhibit complement activation.Such targeted complement-inhibitory strategies have shown promise in improving graft outcomes by inhibiting complement-mediated damage and extending graft survival.This review comprehensively discusses the critical role of complement activation in inducing kidney graft injury with a focus on its role in AMR.By elucidating the detailed mechanisms and contributions of complement pathways,the review seeks to enhance the understanding necessary for developing targeted therapeutic interventions to prevent or treat AMR effectively.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 The Luminex platform,where beads are coated with single human leukocyte antigens(HLA),detects HLA antibodies with higher sensitivity and specificity compared to complement-dependent cytotoxicity(CDC)assay a...BACKGROUND The Luminex platform,where beads are coated with single human leukocyte antigens(HLA),detects HLA antibodies with higher sensitivity and specificity compared to complement-dependent cytotoxicity(CDC)assay and flow crossmatch(FCXM).The clinical significance of donor-specific antibodies(DSAs)detected by this method is still under investigation.AIM To report the impact of low-level pretransplant DSAs detected by the Luminex platform on the rates of acute rejection(AR),allograft function,and long-term graft survival.METHODS This retrospective study was conducted at the Immunology Department of Sindh Institute of Urology and Transplantation,Karachi,Pakistan between January 2013 and December 2022.During this period 2714 patients were transplanted.Out of these patients 78(2.9%)patients had low-level DSAs detected by the Luminex flow beads method and were negative by CDC and FCXM with their donors.All recipients received ABO-compatible live-related kidney transplants.All patients had a minimum follow-up of 1 year.Graft rejection rates,graft function,and patient and graft survival were analyzed.The estimated glomerular filtration rate was calculated by the full CKD-EPI formula.RESULTS The mean age of all recipients was 29.57±10.11 years and 34.53±9.09 years for the donors.In 48(61.5%)patients,the cause of end-stage kidney disease was unknown.DSA against HLA class I was detected in 36(46.1%)patients,class II in 35(44.8%)patients,and both class I and II in 7(8.9%)patients.AR episodes were encountered in 8(10.3%)cases.Seven(87.5%)had T cell mediated rejection(type IA)and one acute antibody-mediated rejection.Antibody status was re-evaluated at the time of biopsy-proven ARs.Five(62.5%)patients lost their DSAs,while three(37.5%)had persistent DSAs.The mean estimated glomerular filtration rate at 1 year was 80.56±27.48 mL/min/1.73 m2 and at the last follow-up 73.41±28.80 mL/min/1.73 m2.The 1-year and 10-year patient and graft survival rates were 99%and 79%and 95%and 75%,respectively.During the follow-up period,10(12.8%)patients died,8 patients had a functioning graft,and 2 patients had failed grafts.Eight patients died due to cardiopulmonary arrest,and two died due to sepsis with failed grafts.CONCLUSION Patients with pretransplant low-level DSAs on Luminex without CDC and FCXM reactivity had good allograft outcomes at 1 year and 10 years as long as they are induced with biological agents and given potent maintenance immunosuppressants.展开更多
Antibodies currently comprise the predominant treatment modality for a variety of diseases;therefore,optimizing their properties rapidly and efficiently is an indispensable step in antibody-based drug development.Insp...Antibodies currently comprise the predominant treatment modality for a variety of diseases;therefore,optimizing their properties rapidly and efficiently is an indispensable step in antibody-based drug development.Inspired by the great success of artificial intelligence-based algorithms,especially deep learning-based methods in the field of biology,various computational methods have been introduced into antibody optimization to reduce costs and increase the success rate of lead candidate generation and optimization.Herein,we briefly review recent progress in deep learning-based antibody optimization,focusing on the available datasets and algorithm input data types that are crucial for constructing appropriate deep learning models.Furthermore,we discuss the current challenges and potential solutions for the future development of general-purpose deep learning algorithms in antibody optimization.展开更多
文摘Targeted treatment of cancer with monoclonal antibodies increases the benefit for patients. In order to improve the anti-tumor activity of monoclonal antibodies, multi-specific antibodies have entered the research field. The emergence of various techniques to produce multi-specific recombinant antibody molecules has led to the selection of target combinations in various forms. To date, only a few multi-specific constructs have entered phase III clinical trials, in contrast to classical monoclonal antibodies. Some of the format options are outlined from a technical point of view. We focus on the achievements and prospects of the underlying technologies for generating biand multispecific antibodies.
基金supported by the National Key Research and Development Program(2023YFD1800501)the National Natural Science Foundation of China(32373030,32202787)+5 种基金the S&T Program of Hebei(21322401D)the Jiangsu Province Natural Sciences Foundation(BK20221432,BK20210158)the Jiangsu Agricultural Science and Technology Innovation Fund(CX(22)3028)the Special Project of Northern Jiangsu(SZ-LYG202109)the Open Fund of Shaoxing Academy of Biomedicine of Zhejiang Sci-Tech University(SXAB202215)the Open Fund of Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases,Ministry of Agriculture and Rural Affairs(YDWS202213).
文摘Porcine deltacoronavirus(PDCoV)is an emerging swine enteropathogenic coronavirus that can cause acute diarrhea and vomiting in newborn piglets and poses a potential risk for cross-species transmission.It is necessary to develop an effective serological diagnostic tool for the surveillance of PDCoV infection and vaccine immunity effects.In this study,we developed a monoclonal antibody-based competitive ELISA(cELISA)that selected the purified recombinant PDCoV nucleocapsid(N)protein as the coating antigen to detect PDCoV antibodies.To evaluate the diagnostic performance of the cELISA,122 swine serum samples(39 positive and 83 negative)were tested and the results were compared with an indirect immunofluorescence assay(IFA)as the reference method.By receiver operating characteristic(ROC)curve analysis,the optimum cutoff value of percent inhibition(PI)was determined to be 26.8%,which showed excellent diagnostic performance,with an area under the curve(AUC)of 0.9919,a diagnostic sensitivity of 97.44%and a diagnostic specificity of 96.34%.Furthermore,there was good agreement between the cELISA and virus neutralization test(VNT)for the detection of PDCoV antibodies,with a coincidence rate of 92.7%,and theκanalysis showed almost perfect agreement(κ=0.851).Overall,the established cELISA showed good diagnostic performance,including sensitivity,specificity and repeatability,and can be used for diagnostic assistance,evaluating the response to vaccination and assessing swine herd immunity.
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.
基金supported by the National Natural Science Foundation of China(Grant No.82272845)the Natural Science Foundation of Shandong(Grant No.ZR2023LZL001)。
文摘As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lung cancer treatment,a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance.Bispecific antibodies(bs Abs)bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles,thus attracting increasing attention as novel antitumor therapies.At present,in addition to the approved bs Ab,amivantamab,three novel bs Abs(KN046,AK112,and SHR-1701)are being evaluated in phase 3 clinical trials and many bs Abs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer(NSCLC).Herein we present the structure,classification,and mechanism of action underlying bs Abs in NSCLC and introduce related clinical trials.Finally,we discuss challenges,potential solutions,and future prospects in the context of cancer treatment with bsAbs.
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[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the potential of polyclonal yolk antibodies(IgY)harvested from laying hens immunized with the rMKIBV vaccine in the prevention and control of IBV.[Methods]The antigenic epitope sequences of IBV,obtained from online databases,were compared with sequences of representative IBV strains from GenBank.Flexible peptides were designed to link all antigenic peptides.The constructed amino acid sequence was analyzed,reverse-translated,codon-optimized,and then inserted into the pET-28a(+)cloning vector.The recombinant vector was introduced into Escherichia coli for expression.The purified,desalted,and endotoxin-removed rMKIBV protein was used as a vaccine to immunize animals for investigation of its immunogenicity and ability to stimulate specific IgY production in laying hens.[Results]The retrieved IBV antigenic epitope sequences showed high similarity with the published N and S protein sequences of 22 representative IBV strains.The predicted isoelectric point and molecular weight of rMKIBV were 10.25 and 63.39 kDa,respectively.The secondary structure of rMKIBV included a high proportion of random coils,which suggested strong antigenicity.High-purity rMKIBV was obtained from E.coli transformed with the recombinant plasmid pET-28a-mkibv.This protein specifically bound to anti-His-tag antibodies,N protein antibodies,and S protein antibodies.The mice immunized with this protein showed increases in the spleen index(P<0.05),elevations in the levels of serum-specific IgG antibodies(P<0.01)and IFN-γ(P<0.05),and no significant change in the IL-2 level.Immunized laying hens successfully produced IgY in egg yolks,with specific IgY antibody levels significantly increasing.Moreover,the IgY antibody titer gradually rose after immunization,reaching the peak after about 50 days and then gradually declining to reach a stable level.[Conclusion]We successfully constructed and expressed the recombinant protein rMKIBV.The protein demonstrated good immunogenicity,stimulating specific antibody production in both mice and laying hens.Notably,the IgY extracted from the yolks of immunized laying hens offers a novel approach to IBV prevention and control.These findings hold significant scientific and practical value for the development of vaccines against IBV.
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 This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with Avacopan.Although relapsing polychondritis has been associated with anti-neutrophil cytoplasmic antibody-associated vasculitis,overlap can result in severe organ involvement,particularly renal damage progressing to end-stage kidney disease.This case presents a unique opportunity to evaluate the potential role of Avacopan as an alternative therapeutic option in managing myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated vasculitis in the context of relapsing polychon-dritis highlighting a positive renal response despite treatment challenges.This is a case of a 69-year-old Caucasian woman who presented to our hospital’s emergency department with a 4 week history of inflammatory polychondritis affecting the auricular cartilage,accompanied by acute kidney injury.On admission,serum creatinine was elevated at 4.0 mg/dL,which progressively increased to 6.07 mg/dL on day 6.The renal biopsy revealed necrotizing and crescentic glomerulonephritis affecting more than 50%of the glomeruli.She was treated with a total of 2500 mg intravenous methylprednisolone over 3 days followed by oral prednisone.Induction treatment included intravenous cyclophosphamide induction,with plans for a total of 2 doses followed by transition to rituximab.However the patient was unable to tolerate rituximab due to allergic reaction so intravenous cyclophosphamide was continued for a total of 6 doses(cumulative dose 3000 mg).In the setting of persistent acute kidney injury,Avacopan was added to the regimen 3 months after diagnosis.Maintenance therapy included azathioprine in addition to Avacopan.Prednisone gradually tapered off at 6 months.CONCLUSION Avacopan may be beneficial in treating anti-neutrophil cytoplasmic antibody-associated vasculitis with coexisting relapsing polychondritis,especially in cases where preservation of kidney function is critical.Further research will be essential to validate these findings and refine treatment protocols for such complex cases.
文摘BACKGROUND Patients with inflammatory bowel diseases(IBD)often miss the scheduled vaccines and have a higher risk of infection susceptibility,including vaccineprevented diseases.AIM To evaluate the vaccine coverage and levels of the post-vaccine antibodies against measles,mumps,rubella,and hepatitis B in children with IBD.METHODS Total 98 patients:46 females(47.2%)and 52 males(52.8%)with IBD(Crohn’s disease-75%and ulcerative colitis-25%)with disease onset age-11.0(6.0;14.0)years whom clinical data,vaccination status and levels of the postvaccination antibodies(IgG)for measles,rubella,mumps,hepatitis B,measured with ELISA were prospectively evaluated.The control group consisted of 88 healthy peers from the biobank data.RESULTS Patients with IBD had lower levels of measles,rubella,and hepatitis B,except mumps,compared to controls.Incomplete vaccination/non-protective titer of the antibodies against measles,mumps rubella,and hepatitis B had 33(33.7%)/52.3%,21(21.4%)/50.4%,26(25.8)/25.6%and 26(25.8%)/55.2%,respectively.Patients with incomplete vaccination had a lower age at the diagnosis for all vaccines.The age of the IBD diagnosis≤6 years was the predictor of incomplete vaccination for measles[odds ratio(OR)=4.6,P=0.001],mumps(OR=5.0,P=0.001),rubella(OR=5.4,P=0.0005)and hepatitis B(OR=5.4,P=0.0005)and corticosteroid treatment for measles(OR=2.2,P=0.074)and mumps(OR=3.0,P=0.047)vaccines.Incomplete vaccination was the predictor of nonprotective titer of antibodies against rubella(OR=6.8,95%CI:2.3-19.9,P=0.0002)/mumps(OR=7.0,95%CI:2.4-20.8;P=0.0002).CONCLUSION Patients with IBD had low vaccine coverage and lower levels of anti-vaccine antibodies against measles,rubella,and hepatitis B.Nearly half of the IBD patients require revaccination.
文摘The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research.Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials,which were selected between 2022 and 2023,in order to understand better the monoclonal antibodies that were most studied.The biopharmaceutical compounds Ibrutinib,Obinutuzumab,Rituximab,Venetoclax,and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications,indicating the importance of amplifying the studies.The action mechanisms that are used imply that their combined use has more success in the disease remission,showing a lower recurrence,adverse effects,and toxicity.Besides the adverse effects and overwhelming prices of the treatment,these immunotherapies results are promising,amplifying the survival rates,improving the patient’s life quality,and resulting in a precision medicine,aiming a custom treatment.The future perspectives on this therapy consist of its application in the public health system,with patients being able to be submitted to this treatment without any costs and receive a better life quality.
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.
基金supported by the UCSI University under the Research Excellence and Innovation Grant(REIG)(grant numbers:REIG-FAS-2023/006,REIG-FAS-2024/001).
文摘Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst min-imising off-target effects.This review provides a comprehensive analysis of ADCs,encompassing their structural components,mechanisms of action,and clinical applications.It also examines recent technological advancements,particularly in antibody engineering and linker design,aimed at enhancing therapeutic efficacy and safety.The current clinical landscape is outlined,highlighting approved ADCs and promising candidates in clinical trials,while also addressing key challenges such as stability,half-life,and systemic toxicity.This review is based on an extensive literature survey from major databases such as Scopus and Web of Science,with a focus on keywords like“antibody-drug conjugates”,“ADC advancements”,and“next-generation ADC technologies”.By integrating insights from both preclinical and clinical perspectives,we highlight the transformative potential of ADCs in advancing modern cancer therapy.
基金supported by the Independent Research and Development Projects Foundation of Shanghai InnoStar Bio-Techology Co.,Ltd.(H23ZZYF01 and H24ZZYF01).
文摘Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics.
文摘Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which recognize and bind to specific target antigens present within the transplanted kidney tissue.Upon binding,these DSAs commonly initiate activation of the complement system within the graft.The activation of the complement cascade sets off a powerful inflammatory response characterized by the recruitment and activation of immune cells,endothelial damage,and subsequent tissue injury.This inflammation underlies many clinical and histological manifestations of AMR,making complement activation a critical player in the disease process.Advancements in our understanding of how complement pathways contribute to kidney graft injury have opened new avenues for therapeutic intervention.Recent research has facilitated the development and application of novel therapies specifically designed to inhibit complement activation.Such targeted complement-inhibitory strategies have shown promise in improving graft outcomes by inhibiting complement-mediated damage and extending graft survival.This review comprehensively discusses the critical role of complement activation in inducing kidney graft injury with a focus on its role in AMR.By elucidating the detailed mechanisms and contributions of complement pathways,the review seeks to enhance the understanding necessary for developing targeted therapeutic interventions to prevent or treat AMR effectively.
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 The Luminex platform,where beads are coated with single human leukocyte antigens(HLA),detects HLA antibodies with higher sensitivity and specificity compared to complement-dependent cytotoxicity(CDC)assay and flow crossmatch(FCXM).The clinical significance of donor-specific antibodies(DSAs)detected by this method is still under investigation.AIM To report the impact of low-level pretransplant DSAs detected by the Luminex platform on the rates of acute rejection(AR),allograft function,and long-term graft survival.METHODS This retrospective study was conducted at the Immunology Department of Sindh Institute of Urology and Transplantation,Karachi,Pakistan between January 2013 and December 2022.During this period 2714 patients were transplanted.Out of these patients 78(2.9%)patients had low-level DSAs detected by the Luminex flow beads method and were negative by CDC and FCXM with their donors.All recipients received ABO-compatible live-related kidney transplants.All patients had a minimum follow-up of 1 year.Graft rejection rates,graft function,and patient and graft survival were analyzed.The estimated glomerular filtration rate was calculated by the full CKD-EPI formula.RESULTS The mean age of all recipients was 29.57±10.11 years and 34.53±9.09 years for the donors.In 48(61.5%)patients,the cause of end-stage kidney disease was unknown.DSA against HLA class I was detected in 36(46.1%)patients,class II in 35(44.8%)patients,and both class I and II in 7(8.9%)patients.AR episodes were encountered in 8(10.3%)cases.Seven(87.5%)had T cell mediated rejection(type IA)and one acute antibody-mediated rejection.Antibody status was re-evaluated at the time of biopsy-proven ARs.Five(62.5%)patients lost their DSAs,while three(37.5%)had persistent DSAs.The mean estimated glomerular filtration rate at 1 year was 80.56±27.48 mL/min/1.73 m2 and at the last follow-up 73.41±28.80 mL/min/1.73 m2.The 1-year and 10-year patient and graft survival rates were 99%and 79%and 95%and 75%,respectively.During the follow-up period,10(12.8%)patients died,8 patients had a functioning graft,and 2 patients had failed grafts.Eight patients died due to cardiopulmonary arrest,and two died due to sepsis with failed grafts.CONCLUSION Patients with pretransplant low-level DSAs on Luminex without CDC and FCXM reactivity had good allograft outcomes at 1 year and 10 years as long as they are induced with biological agents and given potent maintenance immunosuppressants.
基金supported by the National Natural Science Foundation of China(No.12104396)the National Key R&D Program of China(Nos.2021YFF1200404 and 2021YFA1201200)+2 种基金the National Independent Innovation Demonstration Zone Shanghai Zhangjiang Major Projects(No.ZJZX2020014)the Starry Night Science Fund at Shanghai Institute for Advanced Study of Zhejiang University(No.SN-ZJU-SIAS-003)the Shanghai Artificial Intelligence Lab(No.P22KN00272),China.
文摘Antibodies currently comprise the predominant treatment modality for a variety of diseases;therefore,optimizing their properties rapidly and efficiently is an indispensable step in antibody-based drug development.Inspired by the great success of artificial intelligence-based algorithms,especially deep learning-based methods in the field of biology,various computational methods have been introduced into antibody optimization to reduce costs and increase the success rate of lead candidate generation and optimization.Herein,we briefly review recent progress in deep learning-based antibody optimization,focusing on the available datasets and algorithm input data types that are crucial for constructing appropriate deep learning models.Furthermore,we discuss the current challenges and potential solutions for the future development of general-purpose deep learning algorithms in antibody optimization.
