Samar Samoud, Imen Zamali, Fatma Korbi, Ahlem Mtiraoui, Ahlem Ben Hmid, Neila Hannachi, Yousr Galai, Hechmi Louzir, Yousri El Kissi
Background/objectives: Schizophrenia (SZ) is a complex psychiatric disorder with increasing evidence pointing to an autoimmune component, including the presence of antiphospholipid antibodies (aPLs). This study aims to assess the prevalence of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (aβ2GPI) antibodies, particularly the IgG, IgA, and IgM isotypes, in drug-free SZ patients compared to healthy controls, and explore their possible involvement in the disease's pathophysiology.
Methods: Eighty SZ patients meeting DSM-IV criteria were recruited, along with 80 matched healthy controls. Serum samples were analyzed using enzyme-linked immunosorbent assays (ELISA) to quantify IgG, IgA, and IgM isotypes of aCL and aβ2GPI.
Results: SZ patients exhibited significantly higher levels of aCL-IgM and aCL-IgA (p < 0.05), as well as elevated aβ2GPI-IgA (22.5%, p < 0.001), compared to controls. No significant differences were observed in the aCL-IgG isotype. Interestingly, 72% of aPL-positive SZ patients were positive for aβ2GPI-IgA, with some also co-expressing multiple isotypes, suggesting a potential link between SZ and antiphospholipid syndrome (APS).
Conclusions: This study is the first to report a high prevalence of aCL-IgA and aβ2GPI-IgA in SZ patients, highlighting a possible autoimmune involvement in the disease. The presence of multiple aPL isotypes, particularly IgA, suggests a need for further investigation into their role in SZ pathogenesis and their potential association with APS.
{"title":"High Prevalence of aCL-IgA and aβ2GPI-IgA in Drug-Free Schizophrenia Patients: Evidence of a Potential Autoimmune Link.","authors":"Samar Samoud, Imen Zamali, Fatma Korbi, Ahlem Mtiraoui, Ahlem Ben Hmid, Neila Hannachi, Yousr Galai, Hechmi Louzir, Yousri El Kissi","doi":"10.3390/antib13040092","DOIUrl":"10.3390/antib13040092","url":null,"abstract":"<p><strong>Background/objectives: </strong>Schizophrenia (SZ) is a complex psychiatric disorder with increasing evidence pointing to an autoimmune component, including the presence of antiphospholipid antibodies (aPLs). This study aims to assess the prevalence of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (aβ2GPI) antibodies, particularly the IgG, IgA, and IgM isotypes, in drug-free SZ patients compared to healthy controls, and explore their possible involvement in the disease's pathophysiology.</p><p><strong>Methods: </strong>Eighty SZ patients meeting DSM-IV criteria were recruited, along with 80 matched healthy controls. Serum samples were analyzed using enzyme-linked immunosorbent assays (ELISA) to quantify IgG, IgA, and IgM isotypes of aCL and aβ2GPI.</p><p><strong>Results: </strong>SZ patients exhibited significantly higher levels of aCL-IgM and aCL-IgA (<i>p</i> < 0.05), as well as elevated aβ2GPI-IgA (22.5%, <i>p</i> < 0.001), compared to controls. No significant differences were observed in the aCL-IgG isotype. Interestingly, 72% of aPL-positive SZ patients were positive for aβ2GPI-IgA, with some also co-expressing multiple isotypes, suggesting a potential link between SZ and antiphospholipid syndrome (APS).</p><p><strong>Conclusions: </strong>This study is the first to report a high prevalence of aCL-IgA and aβ2GPI-IgA in SZ patients, highlighting a possible autoimmune involvement in the disease. The presence of multiple aPL isotypes, particularly IgA, suggests a need for further investigation into their role in SZ pathogenesis and their potential association with APS.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingzi Liu, Lei Bao, Dharm Sodha, Jing Li, Adrian Mansini, Ali R Djalilian, Xiaoguang Li, Hua Qian, Norito Ishii, Takashi Hashimoto, Kyle T Amber
Background: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. Methods: In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. Results: We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. Conclusions: oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role.
{"title":"Ocular Mucous Membrane Pemphigoid Demonstrates a Distinct Autoantibody Profile from Those of Other Autoimmune Blistering Diseases: A Preliminary Study.","authors":"Yingzi Liu, Lei Bao, Dharm Sodha, Jing Li, Adrian Mansini, Ali R Djalilian, Xiaoguang Li, Hua Qian, Norito Ishii, Takashi Hashimoto, Kyle T Amber","doi":"10.3390/antib13040091","DOIUrl":"10.3390/antib13040091","url":null,"abstract":"<p><p><b>Background</b>: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. <b>Methods</b>: In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. <b>Results</b>: We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. <b>Conclusions</b>: oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review briefly traces the historical development of antibody research and related technologies. The path from early perceptions of immunity to the emergence of modern immunotherapy has been marked by pivotal discoveries and technological advances. Early insights into immunity led to the development of vaccination and serotherapy. The elucidation of antibody structure and function paved the way for monoclonal antibody technology and its application in diagnosis and therapy. Breakthroughs in genetic engineering have enabled the production of humanized antibodies and the advances in Fc engineering, thereby increasing therapeutic efficacy. The discovery of immune checkpoints and cytokines revolutionized the treatment of cancer and autoimmune diseases. The field continues to evolve rapidly with the advent of antibody-drug conjugates, bispecific antibodies, and CAR T-cell therapies. As we face global health challenges, antibody research remains at the forefront of medical innovation and offers promising solutions for the future.
本综述简要回顾了抗体研究和相关技术的历史发展。从早期对免疫的认识到现代免疫疗法的出现,其间充满了关键性的发现和技术进步。对免疫的早期认识促进了疫苗接种和血清疗法的发展。对抗体结构和功能的阐明为单克隆抗体技术及其在诊断和治疗中的应用铺平了道路。基因工程的突破使得人源化抗体的生产和 Fc 工程的进展成为可能,从而提高了疗效。免疫检查点和细胞因子的发现彻底改变了癌症和自身免疫性疾病的治疗。随着抗体药物共轭物、双特异性抗体和 CAR T 细胞疗法的出现,该领域继续快速发展。在我们面临全球健康挑战之际,抗体研究仍处于医学创新的前沿,并为未来提供了前景广阔的解决方案。
{"title":"A Brief Chronicle of Antibody Research and Technological Advances.","authors":"Kazutaka Araki, Ryota Maeda","doi":"10.3390/antib13040090","DOIUrl":"10.3390/antib13040090","url":null,"abstract":"<p><p>This review briefly traces the historical development of antibody research and related technologies. The path from early perceptions of immunity to the emergence of modern immunotherapy has been marked by pivotal discoveries and technological advances. Early insights into immunity led to the development of vaccination and serotherapy. The elucidation of antibody structure and function paved the way for monoclonal antibody technology and its application in diagnosis and therapy. Breakthroughs in genetic engineering have enabled the production of humanized antibodies and the advances in Fc engineering, thereby increasing therapeutic efficacy. The discovery of immune checkpoints and cytokines revolutionized the treatment of cancer and autoimmune diseases. The field continues to evolve rapidly with the advent of antibody-drug conjugates, bispecific antibodies, and CAR T-cell therapies. As we face global health challenges, antibody research remains at the forefront of medical innovation and offers promising solutions for the future.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna N Berlina, Nadezhda S Komova, Kseniya V Serebrennikova, Anatoly V Zherdev, Boris B Dzantiev
When developing immunochemical test systems, it is necessary to obtain specific antibodies. Their quality depends, among other things, on the immunogen used. When preparing hapten-protein conjugates to obtain antibodies for low-molecular-weight compounds, the key factors are the structure of the hapten itself, the presence of a spacer, the size of the carrier protein and the degree of its modification by hapten molecules. This work shows that one additional factor-the conditions for obtaining the hapten-protein conjugate-is overlooked. In this work, we have synthesized conjugates of bisphenol A derivative 4,4-bis(hydroxyphenyl)valeric acid (BVA), the protein carrier soybean trypsin inhibitor (STI), and bovine serum albumin (BSA) in reaction media combining water with two organic solvents: dimethylformamide (DMF) or dimethyl sulfoxide (DMSO). Namely, BSADMF-BVA, STIDMF-BVA, BSADMSO-BVA and STIDMSO-BVA conjugates were obtained. Rabbit polyclonal antibodies against the BSADMF-BVA conjugate demonstrated basically different interactions in the developed ELISA systems using either STIDMF-BVA or STIDMSO-BVA conjugates. The use of the STIDMF-BVA conjugate demonstrated the absence of competition in combination with antisera obtained from BSADMF-BVA in an ELISA. A competitive interaction was observed only with the use of the STIDMSO-BVA conjugate. Under the selected conditions, the detection limit of bisphenol A was 8.3 ng/mL, and the working range of determined concentrations was 18.5-290.3 ng/mL. The obtained data demonstrate the possibility of achieving sensitive immunoassays by simply varying the reaction media for the hapten-protein conjugation, which could provide an additional tool in the development of immunoassays for other low-molecular-weight compounds.
{"title":"Comparison of Conjugates Obtained Using DMSO and DMF as Solvents in the Production of Polyclonal Antibodies and ELISA Development: A Case Study on Bisphenol A.","authors":"Anna N Berlina, Nadezhda S Komova, Kseniya V Serebrennikova, Anatoly V Zherdev, Boris B Dzantiev","doi":"10.3390/antib13040089","DOIUrl":"10.3390/antib13040089","url":null,"abstract":"<p><p>When developing immunochemical test systems, it is necessary to obtain specific antibodies. Their quality depends, among other things, on the immunogen used. When preparing hapten-protein conjugates to obtain antibodies for low-molecular-weight compounds, the key factors are the structure of the hapten itself, the presence of a spacer, the size of the carrier protein and the degree of its modification by hapten molecules. This work shows that one additional factor-the conditions for obtaining the hapten-protein conjugate-is overlooked. In this work, we have synthesized conjugates of bisphenol A derivative 4,4-bis(hydroxyphenyl)valeric acid (BVA), the protein carrier soybean trypsin inhibitor (STI), and bovine serum albumin (BSA) in reaction media combining water with two organic solvents: dimethylformamide (DMF) or dimethyl sulfoxide (DMSO). Namely, BSA<sub>DMF</sub>-BVA, STI<sub>DMF</sub>-BVA, BSA<sub>DMSO</sub>-BVA and STI<sub>DMSO</sub>-BVA conjugates were obtained. Rabbit polyclonal antibodies against the BSA<sub>DMF</sub>-BVA conjugate demonstrated basically different interactions in the developed ELISA systems using either STI<sub>DMF</sub>-BVA or STI<sub>DMSO</sub>-BVA conjugates. The use of the STI<sub>DMF</sub>-BVA conjugate demonstrated the absence of competition in combination with antisera obtained from BSA<sub>DMF</sub>-BVA in an ELISA. A competitive interaction was observed only with the use of the STI<sub>DMSO</sub>-BVA conjugate. Under the selected conditions, the detection limit of bisphenol A was 8.3 ng/mL, and the working range of determined concentrations was 18.5-290.3 ng/mL. The obtained data demonstrate the possibility of achieving sensitive immunoassays by simply varying the reaction media for the hapten-protein conjugation, which could provide an additional tool in the development of immunoassays for other low-molecular-weight compounds.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/Objectives: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal-epithelial transition (MET) gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, and gene amplification, many of which arise as resistance mechanisms to other oncogenic drivers like epidermal growth factor receptor (EGFR) mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. Methods: A comprehensive literature search was conducted using major medical databases looking at key relevant studies on anti-MET antibody studies. Both authors reviewed the literature, assessed study quality, and interpreted the results from each study. Results: Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody. Conclusions: MET plays a significant role in NSCLC and amivantamab along with other anti-MET targeted therapies play a role in directly targeting MET and addressing acquired resistance to oncogenic drivers. Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes.
背景/目标:非小细胞肺癌(NSCLC)仍然是全球癌症死亡的主要原因,尽管靶向疗法的进步改善了治疗效果。间质-上皮转化(MET)基因在 NSCLC 中发挥着重要作用,通常是通过蛋白过表达、第 14 号外显子跳越突变和基因扩增等方式实现的,其中许多是作为表皮生长因子受体(EGFR)突变等其他致癌驱动因素的耐药机制而出现的。本综述探讨了抗MET抗体疗法的发展和临床疗效。方法:利用主要医学数据库对抗MET抗体研究的主要相关研究进行了全面的文献检索。两位作者审阅了文献,评估了研究质量,并解释了每项研究的结果。研究结果Amivantamab是一种双特异性表皮生长因子受体/MET抗体,已被批准用于治疗表皮生长因子受体外显子20插入,最近又扩展到针对奥希替尼治疗进展的表皮生长因子受体经典突变。其他正在开发的重要抗MET靶向疗法包括抗体药物共轭物,如telisotuzumab vedotin、REGN5093-M114、AZD9592和emibetuzumab,后者是一种人源化免疫球蛋白G4单克隆双价MET抗体。结论MET在NSCLC中发挥着重要作用,阿米万他单抗和其他抗MET靶向疗法在直接靶向MET和解决对致癌驱动因素的获得性耐药性方面发挥着作用。未来的研究应侧重于开发新型 MET 抗体药物和探索新的治疗组合,以提高疗效并克服 NSCLC 的耐药性。完善生物标志物驱动的方法以确保精确选择患者也是优化治疗效果的关键。
{"title":"Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions.","authors":"Kinsley Wang, Robert Hsu","doi":"10.3390/antib13040088","DOIUrl":"https://doi.org/10.3390/antib13040088","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal-epithelial transition (<i>MET</i>) gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, and gene amplification, many of which arise as resistance mechanisms to other oncogenic drivers like epidermal growth factor receptor (<i>EGFR</i>) mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. <b>Methods:</b> A comprehensive literature search was conducted using major medical databases looking at key relevant studies on anti-MET antibody studies. Both authors reviewed the literature, assessed study quality, and interpreted the results from each study. <b>Results:</b> Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody. <b>Conclusions:</b> MET plays a significant role in NSCLC and amivantamab along with other anti-MET targeted therapies play a role in directly targeting MET and addressing acquired resistance to oncogenic drivers. Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Janna Bashar, Zihao Zheng, Aisha M Mergaert, Ryan R Adyniec, Srishti Gupta, Maya F Amjadi, Sara S McCoy, Michael A Newton, Miriam A Shelef
Background: Autoantibodies are commonly used as biomarkers in autoimmune diseases, but there are limitations. For example, autoantibody biomarkers have poor sensitivity or specificity in systemic lupus erythematosus and do not exist in the spondyloarthropathies, impairing diagnosis and treatment. While autoantibodies suitable for strong biomarkers may not exist in these conditions, another possibility is that technology has limited their discovery. The purpose of this study was to use a novel high-density peptide array that enables the evaluation of IgG binding to every possible linear antigen in the entire human peptidome, as well as a novel machine learning approach that incorporates ELISA validation predictability in order to discover autoantibodies that could be developed into sensitive and specific markers of lupus or spondyloarthropathy.
Methods: We used a peptide array containing the human peptidome, several viral peptidomes, and key post-translational modifications (6 million peptides) to quantify IgG binding in lupus, spondyloarthropathy, rheumatoid arthritis, Sjögren's disease, and control sera. Using ELISA data for 70 peptides, we performed a random forest analysis that evaluated multiple array features to predict which peptides might be good biomarkers, as confirmed by ELISA. We validated the peptide prediction methodology in rheumatoid arthritis and COVID-19, conditions for which the antibody repertoire is well-understood, and then evaluated IgG binding by ELISA to peptides that we predicted would be highly bound specifically in lupus or spondyloarthropathy.
Results: Our methodology performed well in validation studies, but peptides predicted to be highly and specifically bound in lupus or spondyloarthropathy could not be confirmed by ELISA.
Conclusions: In a comprehensive evaluation of the entire human peptidome, highly sensitive and specific IgG autoantibodies were not identified in lupus or spondyloarthropathy. Thus, the pathogenesis of lupus and spondyloarthropathy may not depend upon unique autoantigens, and other types of molecules should be sought as optimal biomarkers in these conditions.
{"title":"Limited Biomarker Potential for IgG Autoantibodies Reactive to Linear Epitopes in Systemic Lupus Erythematosus or Spondyloarthropathy.","authors":"S Janna Bashar, Zihao Zheng, Aisha M Mergaert, Ryan R Adyniec, Srishti Gupta, Maya F Amjadi, Sara S McCoy, Michael A Newton, Miriam A Shelef","doi":"10.3390/antib13040087","DOIUrl":"https://doi.org/10.3390/antib13040087","url":null,"abstract":"<p><strong>Background: </strong>Autoantibodies are commonly used as biomarkers in autoimmune diseases, but there are limitations. For example, autoantibody biomarkers have poor sensitivity or specificity in systemic lupus erythematosus and do not exist in the spondyloarthropathies, impairing diagnosis and treatment. While autoantibodies suitable for strong biomarkers may not exist in these conditions, another possibility is that technology has limited their discovery. The purpose of this study was to use a novel high-density peptide array that enables the evaluation of IgG binding to every possible linear antigen in the entire human peptidome, as well as a novel machine learning approach that incorporates ELISA validation predictability in order to discover autoantibodies that could be developed into sensitive and specific markers of lupus or spondyloarthropathy.</p><p><strong>Methods: </strong>We used a peptide array containing the human peptidome, several viral peptidomes, and key post-translational modifications (6 million peptides) to quantify IgG binding in lupus, spondyloarthropathy, rheumatoid arthritis, Sjögren's disease, and control sera. Using ELISA data for 70 peptides, we performed a random forest analysis that evaluated multiple array features to predict which peptides might be good biomarkers, as confirmed by ELISA. We validated the peptide prediction methodology in rheumatoid arthritis and COVID-19, conditions for which the antibody repertoire is well-understood, and then evaluated IgG binding by ELISA to peptides that we predicted would be highly bound specifically in lupus or spondyloarthropathy.</p><p><strong>Results: </strong>Our methodology performed well in validation studies, but peptides predicted to be highly and specifically bound in lupus or spondyloarthropathy could not be confirmed by ELISA.</p><p><strong>Conclusions: </strong>In a comprehensive evaluation of the entire human peptidome, highly sensitive and specific IgG autoantibodies were not identified in lupus or spondyloarthropathy. Thus, the pathogenesis of lupus and spondyloarthropathy may not depend upon unique autoantigens, and other types of molecules should be sought as optimal biomarkers in these conditions.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions.
Methods: A comprehensive literature search was conducted in major medical databases through July 2024. Relevant studies on monoclonal antibodies for intraocular diseases were included. Two independent researchers screened the literature, extracted data, and assessed study quality. Cost-effectiveness analyses were also reviewed.
Results: Anti-vascular endothelial growth factor (VEGF) antibodies, such as bevacizumab, ranibizumab, and aflibercept, showed significant therapeutic effects in neovascular age-related macular degeneration (NVAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Tumor necrosis factor-alpha (TNF-α) inhibitors demonstrated promising results in treating noninfectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios.
Conclusions: Monoclonal antibodies are vital for treating intraocular diseases, but continuous innovation and rigorous clinical evaluation are essential. Future research should focus on developing novel delivery systems, exploring combination therapies, conducting long-term follow-up studies, and investigating personalized treatment strategies to provide safer, more effective, and cost-effective therapeutic solutions.
{"title":"Ophthalmic Use of Targeted Biologics in the Management of Intraocular Diseases: Current and Emerging Therapies.","authors":"Yuan Zong, Miki Miyagaki, Mingming Yang, Jing Zhang, Yaru Zou, Kyoko Ohno-Matsui, Koju Kamoi","doi":"10.3390/antib13040086","DOIUrl":"https://doi.org/10.3390/antib13040086","url":null,"abstract":"<p><strong>Background: </strong>Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in major medical databases through July 2024. Relevant studies on monoclonal antibodies for intraocular diseases were included. Two independent researchers screened the literature, extracted data, and assessed study quality. Cost-effectiveness analyses were also reviewed.</p><p><strong>Results: </strong>Anti-vascular endothelial growth factor (VEGF) antibodies, such as bevacizumab, ranibizumab, and aflibercept, showed significant therapeutic effects in neovascular age-related macular degeneration (NVAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Tumor necrosis factor-alpha (TNF-α) inhibitors demonstrated promising results in treating noninfectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios.</p><p><strong>Conclusions: </strong>Monoclonal antibodies are vital for treating intraocular diseases, but continuous innovation and rigorous clinical evaluation are essential. Future research should focus on developing novel delivery systems, exploring combination therapies, conducting long-term follow-up studies, and investigating personalized treatment strategies to provide safer, more effective, and cost-effective therapeutic solutions.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michelle L McKeague, Jason Lohmueller, Matthew T Dracz, Najla Saadallah, Eric D Ricci, Donella M Beckwith, Ramya Ayyalasomayajula, Maré Cudic, Olivera J Finn
Background/objectives: Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high risk for colon cancer were enrolled in a clinical trial to evaluate the feasibility of using a MUC1 peptide vaccine to prevent colon cancer. Anti-MUC1 antibodies elicited by this vaccine were cloned using peripheral blood B cells and sera collected two weeks after a one-year booster. Twelve of these fully human monoclonal antibodies (mAb) were tested for binding to MUC1+ target cells, and three with the highest binding were further evaluated for various effector functions important for tumor rejection.
Methods: Immune cells were incubated together with target cells expressing variations in the number, distance, and membrane anchoring properties of the MUC1 epitope in the presence of each mAb.
Results: All three mAbs mediated antibody-dependent cytokine release (ADCR), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Two also mediated antibody-dependent trogocytosis/trogoptosis (ADCT). None were capable of complement-dependent cytotoxicity (CDC).
Conclusions: ADCP and ADCT functions were more efficient when antibodies bound epitopes proximal to and anchored to the membrane, providing insight for future therapeutic antibody validation strategies.
背景/目的:粘蛋白-1(MUC1)是一种跨膜糖蛋白,与正常细胞相比,它在癌前病变和恶性上皮细胞中过度表达且糖基化过低,从而成为体液免疫和细胞免疫的靶抗原。有晚期结肠腺瘤病史和结肠癌高风险的健康人参加了一项临床试验,以评估使用 MUC1 肽疫苗预防结肠癌的可行性。使用外周血 B 细胞和一年强化治疗两周后收集的血清克隆了该疫苗激发的抗 MUC1 抗体。对其中 12 种全人源单克隆抗体(mAb)与 MUC1+ 靶细胞的结合力进行了测试,并对结合力最高的 3 种单克隆抗体进一步评估了其对肿瘤排斥的各种效应功能:方法:在每种 mAb 存在的情况下,将免疫细胞与表达不同数量、距离和膜锚定特性的 MUC1 表位的靶细胞一起孵育:结果:所有三种 mAb 都能介导抗体依赖性细胞因子释放(ADCR)、抗体依赖性细胞毒性(ADCC)和抗体依赖性细胞吞噬(ADCP)。其中两种还介导了抗体依赖性逆细胞吞噬/凋亡(ADCT)。结论:ADCP和ADCT功能在抗体结合近端表位并锚定在膜上时更有效,这为未来的治疗性抗体验证策略提供了启示。
{"title":"Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions.","authors":"Michelle L McKeague, Jason Lohmueller, Matthew T Dracz, Najla Saadallah, Eric D Ricci, Donella M Beckwith, Ramya Ayyalasomayajula, Maré Cudic, Olivera J Finn","doi":"10.3390/antib13040085","DOIUrl":"10.3390/antib13040085","url":null,"abstract":"<p><strong>Background/objectives: </strong>Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high risk for colon cancer were enrolled in a clinical trial to evaluate the feasibility of using a MUC1 peptide vaccine to prevent colon cancer. Anti-MUC1 antibodies elicited by this vaccine were cloned using peripheral blood B cells and sera collected two weeks after a one-year booster. Twelve of these fully human monoclonal antibodies (mAb) were tested for binding to MUC1+ target cells, and three with the highest binding were further evaluated for various effector functions important for tumor rejection.</p><p><strong>Methods: </strong>Immune cells were incubated together with target cells expressing variations in the number, distance, and membrane anchoring properties of the MUC1 epitope in the presence of each mAb.</p><p><strong>Results: </strong>All three mAbs mediated antibody-dependent cytokine release (ADCR), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Two also mediated antibody-dependent trogocytosis/trogoptosis (ADCT). None were capable of complement-dependent cytotoxicity (CDC).</p><p><strong>Conclusions: </strong>ADCP and ADCT functions were more efficient when antibodies bound epitopes proximal to and anchored to the membrane, providing insight for future therapeutic antibody validation strategies.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Inés Klepp, Federico Carlos Blanco, María Mercedes Bigi, Cristina Lourdes Vázquez, Elizabeth Andrea García, Julia Sabio Y García, Fabiana Bigi
The development of vaccines and effective diagnostic methods for bovine tuberculosis requires an understanding of the immune response against its causative agent, Mycobacterium bovis. Although this disease is primarily investigated and diagnosed through the assessment of cell-mediated immunity, the role of B cells and antibodies in bovine tuberculosis has been relatively undervalued and understudied. Current evidence indicates that circulating M. bovis-specific antibodies are not effective in controlling the disease. However, local humoral immune responses may contribute to either defence or pathology. Recent studies in animal models and cattle vaccine trials suggest a potential beneficial role of B cells in tuberculosis control. This review discusses the role of B cells and antibodies in bovine tuberculosis and explores antibody-based diagnostics for the disease, including traditional techniques, such as different ELISA, new platforms based on multiple antigens and point-of-care technologies. The high specificity and sensitivity values achieved by numerous antibody-based tests support their use as complementary tests for the diagnosis of bovine tuberculosis, especially for identifying infected animals that may be missed by the official tests.
要开发牛结核病疫苗和有效的诊断方法,就必须了解牛结核病致病菌牛分枝杆菌的免疫反应。虽然这种疾病主要是通过评估细胞介导免疫进行调查和诊断的,但 B 细胞和抗体在牛结核病中的作用却相对被低估,研究也相对不足。目前的证据表明,循环中的牛结核杆菌特异性抗体不能有效控制疾病。然而,局部体液免疫反应可能有助于疾病的防御或病理变化。最近在动物模型和牛疫苗试验中进行的研究表明,B 细胞在结核病控制中可能起到有益的作用。本综述讨论了 B 细胞和抗体在牛结核病中的作用,并探讨了基于抗体的疾病诊断方法,包括传统技术(如不同的 ELISA)、基于多种抗原的新平台和护理点技术。许多基于抗体的检测方法都具有很高的特异性和灵敏度,支持将其作为诊断牛结核病的辅助检测方法,特别是用于识别官方检测方法可能漏检的受感染动物。
{"title":"B Cell and Antibody Responses in Bovine Tuberculosis.","authors":"Laura Inés Klepp, Federico Carlos Blanco, María Mercedes Bigi, Cristina Lourdes Vázquez, Elizabeth Andrea García, Julia Sabio Y García, Fabiana Bigi","doi":"10.3390/antib13040084","DOIUrl":"https://doi.org/10.3390/antib13040084","url":null,"abstract":"<p><p>The development of vaccines and effective diagnostic methods for bovine tuberculosis requires an understanding of the immune response against its causative agent, <i>Mycobacterium bovis</i>. Although this disease is primarily investigated and diagnosed through the assessment of cell-mediated immunity, the role of B cells and antibodies in bovine tuberculosis has been relatively undervalued and understudied. Current evidence indicates that circulating <i>M. bovis</i>-specific antibodies are not effective in controlling the disease. However, local humoral immune responses may contribute to either defence or pathology. Recent studies in animal models and cattle vaccine trials suggest a potential beneficial role of B cells in tuberculosis control. This review discusses the role of B cells and antibodies in bovine tuberculosis and explores antibody-based diagnostics for the disease, including traditional techniques, such as different ELISA, new platforms based on multiple antigens and point-of-care technologies. The high specificity and sensitivity values achieved by numerous antibody-based tests support their use as complementary tests for the diagnosis of bovine tuberculosis, especially for identifying infected animals that may be missed by the official tests.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaotian Zhong, Guoying Grace Yan, Apurva Chaturvedi, Xiuling Li, Yijie Gao, Mahasweta Girgenrath, Chris J Corcoran, Liz Diblasio-Smith, Edward R LaVallie, Teresse de Rham, Jing Zhou, Molica Abel, Logan Riegel, Sean K H Lim, Laird Bloom, Laura Lin, Aaron M D'Antona
Background: α-dystroglycanopathies are congenital muscular dystrophies in which genetic mutations cause the decrease or absence of a unique and complex O-linked glycan called matriglycan. This hypoglycosylation of O-linked matriglycan on the α-dystroglycan (α-DG) protein subunit abolishes or reduces the protein binding to extracellular ligands such as laminins in skeletal muscles, leading to compromised survival of muscle cells after contraction. Methods: Surrogate molecular linkers reconnecting laminin-211 and the dystroglycan β-subunit through bispecific antibodies can be engineered to improve muscle function in the α-dystroglycanopathies. This study reports the metabolic engineering of a novel glycofusion bispecific (GBi) antibody that fuses the mucin-like domain of the α-DG to the light chain of an anti-β-DG subunit antibody. Results: Transient HEK production with the co-transfection of LARGE1, the glycoenzyme responsible for the matriglycan modification, produced the GBi antibody only with a light matriglycan modification and a weak laminin-211 binding activity. However, when a sugar feed mixture of uridine, galactose, and manganese ion (Mn2+) was added to the culture medium, the GBi antibody produced exhibited a dramatically enhanced matriglycan modification and a much stronger laminin-binding activity. Conclusions: Further investigation has revealed that Mn2+ in the sugar feeds played a critical role in increasing the matriglycan modification of the GBi antibody, key for the function of the resulting bispecific antibody.
{"title":"Metabolic Engineering of Glycofusion Bispecific Antibodies for α-Dystroglycanopathies.","authors":"Xiaotian Zhong, Guoying Grace Yan, Apurva Chaturvedi, Xiuling Li, Yijie Gao, Mahasweta Girgenrath, Chris J Corcoran, Liz Diblasio-Smith, Edward R LaVallie, Teresse de Rham, Jing Zhou, Molica Abel, Logan Riegel, Sean K H Lim, Laird Bloom, Laura Lin, Aaron M D'Antona","doi":"10.3390/antib13040083","DOIUrl":"https://doi.org/10.3390/antib13040083","url":null,"abstract":"<p><p><b>Background:</b> α-dystroglycanopathies are congenital muscular dystrophies in which genetic mutations cause the decrease or absence of a unique and complex O-linked glycan called matriglycan. This hypoglycosylation of O-linked matriglycan on the α-dystroglycan (α-DG) protein subunit abolishes or reduces the protein binding to extracellular ligands such as laminins in skeletal muscles, leading to compromised survival of muscle cells after contraction. <b>Methods:</b> Surrogate molecular linkers reconnecting laminin-211 and the dystroglycan β-subunit through bispecific antibodies can be engineered to improve muscle function in the α-dystroglycanopathies. This study reports the metabolic engineering of a novel glycofusion bispecific (GBi) antibody that fuses the mucin-like domain of the α-DG to the light chain of an anti-β-DG subunit antibody. <b>Results:</b> Transient HEK production with the co-transfection of LARGE1, the glycoenzyme responsible for the matriglycan modification, produced the GBi antibody only with a light matriglycan modification and a weak laminin-211 binding activity. However, when a sugar feed mixture of uridine, galactose, and manganese ion (Mn<sup>2+</sup>) was added to the culture medium, the GBi antibody produced exhibited a dramatically enhanced matriglycan modification and a much stronger laminin-binding activity. <b>Conclusions:</b> Further investigation has revealed that Mn<sup>2+</sup> in the sugar feeds played a critical role in increasing the matriglycan modification of the GBi antibody, key for the function of the resulting bispecific antibody.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}