Frontiers in Immunology最新文献

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Molecular mimicry of SARS-COV-2 antigens as a possible natural anti-cancer preventive immunization 将 SARS-COV-2 抗原的分子模拟作为一种可能的天然抗癌预防性免疫方法
Frontiers in Immunology Pub Date : 2024-06-14 DOI: 10.3389/fimmu.2024.1398002
Concetta Ragone, A. Mauriello, Beatrice Cavalluzzo, Ernesta Cavalcanti, Luigi Russo, Carmen Manolio, Simona Mangano, B. Cembrola, M. Tagliamonte, Luigi Buonaguro
{"title":"Molecular mimicry of SARS-COV-2 antigens as a possible natural anti-cancer preventive immunization","authors":"Concetta Ragone, A. Mauriello, Beatrice Cavalluzzo, Ernesta Cavalcanti, Luigi Russo, Carmen Manolio, Simona Mangano, B. Cembrola, M. Tagliamonte, Luigi Buonaguro","doi":"10.3389/fimmu.2024.1398002","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1398002","url":null,"abstract":"In the present study we investigated whether peptides derived from the entire SARS-CoV-2 proteome share homology to TAAs (tumor-associated antigens) and cross-reactive CD8+ T cell can be elicited by the BNT162b2 preventive vaccine or the SARS-CoV-2 natural infection.Viral epitopes with high affinity (<100nM) to the HLA-A*02:01 allele were predicted. Shared and variant-specific epitopes were identified. Significant homologies in amino acidic sequence have been found between SARS-CoV-2 peptides and multiple TAAs, mainly associated with breast, liver, melanoma and colon cancers. The molecular mimicry of the viral epitopes and the TAAs was found in all viral proteins, mostly the Orf 1ab and the Spike, which is included in the BNT162b2 vaccine. Predicted structural similarities confirmed the sequence homology and comparable patterns of contact with both HLA and TCR α and β chains were observed. CD8+ T cell clones cross-reactive with the paired peptides have been found by MHC class l-dextramer staining. Our results show for the first time that several SARS-COV-2 antigens are highly homologous to TAAs and cross-reactive T cells are identified in infected and BNT162b2 preventive vaccinated individuals. The implication would be that the SARS-Cov-2 pandemic could represent a natural preventive immunization for breast, liver, melanoma and colon cancers. In the coming years, real-world evidences will provide the final proof for such immunological experimental evidence. Moreover, such SARS-CoV-2 epitopes can be used to develop “multi-cancer” off-the-shelf preventive/therapeutic vaccine formulations, with higher antigenicity and immunogenicity than over-expressed tumor self-antigens, for the potential valuable benefit of thousands of cancer patients around the World.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"18 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141343159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detailed phenotyping reveals diverse and highly skewed neutrophil subsets in both the blood and airways during active tuberculosis infection 详细的表型分析表明,在活动性肺结核感染期间,血液和呼吸道中的中性粒细胞亚群多种多样且高度倾斜
Frontiers in Immunology Pub Date : 2024-06-14 DOI: 10.3389/fimmu.2024.1422836
Shepherd Nhamoyebonde, Mark Chambers, Lerato Ndlovu, F. Karim, M. Mazibuko, Z. Mhlane, Lindiwe Madziwa, Yunus Moosa, S. Moodley, Monjurul Hoque, Al Leslie
{"title":"Detailed phenotyping reveals diverse and highly skewed neutrophil subsets in both the blood and airways during active tuberculosis infection","authors":"Shepherd Nhamoyebonde, Mark Chambers, Lerato Ndlovu, F. Karim, M. Mazibuko, Z. Mhlane, Lindiwe Madziwa, Yunus Moosa, S. Moodley, Monjurul Hoque, Al Leslie","doi":"10.3389/fimmu.2024.1422836","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1422836","url":null,"abstract":"Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease.To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa.Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1.Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141341428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune interactions and regulation with CD39+ extracellular vesicles from platelet concentrates 血小板浓缩物中 CD39+ 细胞外小泡的免疫相互作用和调节作用
Frontiers in Immunology Pub Date : 2024-06-14 DOI: 10.3389/fimmu.2024.1397967
Adèle Silane Delorme, Alexandra Laguide, Marie Tamagne, M. Pinheiro, Léonie Cagnet, Deborah Neyrinck-Leglantier, Mehdi Khelfa, Sabine Cleophax, France Pirenne, Benoît Vingert
{"title":"Immune interactions and regulation with CD39+ extracellular vesicles from platelet concentrates","authors":"Adèle Silane Delorme, Alexandra Laguide, Marie Tamagne, M. Pinheiro, Léonie Cagnet, Deborah Neyrinck-Leglantier, Mehdi Khelfa, Sabine Cleophax, France Pirenne, Benoît Vingert","doi":"10.3389/fimmu.2024.1397967","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1397967","url":null,"abstract":"CD39 plays an important role in the immunoregulation and inhibition of effector cells. It is expressed on immune cells, including Tregs, and on extracellular vesicles (EVs) budding from the plasma membrane. Platelet transfusion may induce alloimmunization against HLA-I antigens, leading to refractoriness to platelet transfusion with severe consequences for patients. Tregs may play a key role in determining whether alloimmunization occurs in patients with hematologic disorders. We hypothesized that CD39+ EVs might play an immunoregulatory role, particularly in the context of platelet transfusions in patients with hematologic disorders. Such alloimmunization leads to the production of alloantibodies and is sensitive to the regulatory action of CD39.We characterized CD39+ EVs in platelet concentrates by flow cytometry. The absolute numbers and cellular origins of CD39+ EVs were evaluated. We also performed functional tests to evaluate interactions with immune cells and their functions.We found that CD39+ EVs from platelet concentrates had an inhibitory phenotype that could be transferred to the immune cells with which they interacted: CD4+ and CD8+ T lymphocytes (TLs), dendritic cells, monocytes, and B lymphocytes (BLs). Moreover, the concentration of CD39+ EVs in platelet concentrates varied and was very high in 10% of concentrates. The number of these EVs present was determinant for EV-cell interactions. Finally, functional interactions were observed with BLs, CD4+ TLs and CD39+ EVs for immunoglobulin production and lymphoproliferation, with potential implications for the immunological management of patients.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"25 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141340456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial: Programmed cell death in aquatic animals 社论:水生动物的程序性细胞死亡
Frontiers in Immunology Pub Date : 2024-06-14 DOI: 10.3389/fimmu.2024.1428742
Qingchao Wang, Dahai Yang, Linlin Zhang, Madison Powell, Yu-Hung Lin
{"title":"Editorial: Programmed cell death in aquatic animals","authors":"Qingchao Wang, Dahai Yang, Linlin Zhang, Madison Powell, Yu-Hung Lin","doi":"10.3389/fimmu.2024.1428742","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1428742","url":null,"abstract":"","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"32 44","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141340378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of functional enhancer variants associated with type I diabetes in CD4+ T cells 鉴定 CD4+ T 细胞中与 I 型糖尿病相关的功能增强子变体
Frontiers in Immunology Pub Date : 2024-06-14 DOI: 10.3389/fimmu.2024.1387253
Arpit Mishra, Ajay Jajodia, Eryn Weston, N. Jayavelu, Mariana Garcia, Daniel Hossack, R. D. Hawkins
{"title":"Identification of functional enhancer variants associated with type I diabetes in CD4+ T cells","authors":"Arpit Mishra, Ajay Jajodia, Eryn Weston, N. Jayavelu, Mariana Garcia, Daniel Hossack, R. D. Hawkins","doi":"10.3389/fimmu.2024.1387253","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1387253","url":null,"abstract":"Type I diabetes is an autoimmune disease mediated by T-cell destruction of β cells in pancreatic islets. Currently, there is no known cure, and treatment consists of daily insulin injections. Genome-wide association studies and twin studies have indicated a strong genetic heritability for type I diabetes and implicated several genes. As most strongly associated variants are noncoding, there is still a lack of identification of functional and, therefore, likely causal variants. Given that many of these genetic variants reside in enhancer elements, we have tested 121 CD4+ T-cell enhancer variants associated with T1D. We found four to be functional through massively parallel reporter assays. Three of the enhancer variants weaken activity, while the fourth strengthens activity. We link these to their cognate genes using 3D genome architecture or eQTL data and validate them using CRISPR editing. Validated target genes include CLEC16A and SOCS1. While these genes have been previously implicated in type 1 diabetes and other autoimmune diseases, we show that enhancers controlling their expression harbor functional variants. These variants, therefore, may act as causal type 1 diabetic variants.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141343933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Second bone marrow transplantation into regenerating hematopoiesis enhances reconstitution of immune system 向再生造血系统进行第二次骨髓移植可加强免疫系统的重建
Frontiers in Immunology Pub Date : 2024-06-14 DOI: 10.3389/fimmu.2024.1405210
Kateřina Faltusová, Martin Báječný, Tomáš Heizer, Petr Páral, Chia-Ling Chen, Katarína Szikszai, Pavel Klener, Emanuel Nečas
{"title":"Second bone marrow transplantation into regenerating hematopoiesis enhances reconstitution of immune system","authors":"Kateřina Faltusová, Martin Báječný, Tomáš Heizer, Petr Páral, Chia-Ling Chen, Katarína Szikszai, Pavel Klener, Emanuel Nečas","doi":"10.3389/fimmu.2024.1405210","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1405210","url":null,"abstract":"In bone marrow transplantation (BMT), hematopoiesis-reconstituting cells are introduced following myeloablative treatment, which eradicates existing hematopoietic cells and disrupts stroma within the hematopoietic tissue. Both hematopoietic cells and stroma then undergo regeneration. Our study compares the outcomes of a second BMT administered to mice shortly after myeloablative treatment and the first BMT, with those of a second BMT administered to mice experiencing robust hematopoietic regeneration after the initial transplant. We evaluated the efficacy of the second BMT in terms of engraftment efficiency, types of generated blood cells, and longevity of function. Our findings show that regenerating hematopoiesis readily accommodates newly transplanted stem cells, including those endowed with a robust capacity for generating B and T cells. Importantly, our investigation uncovered a window for preferential engraftment of transplanted stem cells coinciding with the resumption of blood cell production. Repeated BMT could intensify hematopoiesis reconstitution and enable therapeutic administration of genetically modified autologous stem cells.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"48 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141339629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma 基于增强计算机断层扫描的机器学习放射组学预测可切除食管鳞状细胞癌的新辅助免疫疗法
Frontiers in Immunology Pub Date : 2024-06-14 DOI: 10.3389/fimmu.2024.1405146
Jia-Ling Wang, Lian-Sha Tang, Xia Zhong, Yi Wang, Yu Feng, Yun Zhang, Ji-Yan Liu
{"title":"A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma","authors":"Jia-Ling Wang, Lian-Sha Tang, Xia Zhong, Yi Wang, Yu Feng, Yun Zhang, Ji-Yan Liu","doi":"10.3389/fimmu.2024.1405146","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1405146","url":null,"abstract":"Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients.This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models.One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87–0.99) and 0.85 (95% CI 0.69–1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model.Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141344668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vaccines for Streptococcus agalactiae: current status and future perspectives 无乳链球菌疫苗:现状与未来展望
Frontiers in Immunology Pub Date : 2024-06-14 DOI: 10.3389/fimmu.2024.1430901
João Matheus Sobral Pena, Pamella Silva Lannes-Costa, P. E. Nagao
{"title":"Vaccines for Streptococcus agalactiae: current status and future perspectives","authors":"João Matheus Sobral Pena, Pamella Silva Lannes-Costa, P. E. Nagao","doi":"10.3389/fimmu.2024.1430901","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1430901","url":null,"abstract":"A maternal vaccine to protect newborns against invasive Streptococcus agalactiae infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy and induce strong immune responses and placental transfer of protective antibodies. Polysaccharide vaccines against S. agalactiae conjugated to protein carriers are in advanced stages of development. Additionally, protein-based vaccines are also in development, showing great promise as they can provide protection regardless of serotype. Furthermore, safety concerns regarding a new vaccine are the main barriers identified. Here, we present vaccines in development and identified safety, cost, and efficacy concerns, especially in high-need, low-income countries.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"10 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141339061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Individualized neoantigen peptide immunization of a metastatic pancreatic cancer patient: a case report of combined tumor and liquid biopsy 一名转移性胰腺癌患者的个体化新抗原肽免疫:肿瘤和液体活检联合病例报告
Frontiers in Immunology Pub Date : 2024-06-13 DOI: 10.3389/fimmu.2024.1414737
Tim Roehnisch, Mari Carmen Martos-Contreras, Mehdi Manoochehri, Mauro Nogueira, Franziska Bremm, Jan Dörrie, Jan Christoph, Meik Kunz, W. Schönharting
{"title":"Individualized neoantigen peptide immunization of a metastatic pancreatic cancer patient: a case report of combined tumor and liquid biopsy","authors":"Tim Roehnisch, Mari Carmen Martos-Contreras, Mehdi Manoochehri, Mauro Nogueira, Franziska Bremm, Jan Dörrie, Jan Christoph, Meik Kunz, W. Schönharting","doi":"10.3389/fimmu.2024.1414737","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1414737","url":null,"abstract":"This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"54 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141346853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disease-specific autoantibody production in the lungs and salivary glands of anti-synthetase syndrome 抗合成酶综合征患者肺部和唾液腺中产生的疾病特异性自身抗体
Frontiers in Immunology Pub Date : 2024-06-13 DOI: 10.3389/fimmu.2024.1265792
M. Takeshita, Katsuya Suzuki, M. Nakazawa, H. Kamata, Makoto Ishii, Y. Oyamada, Hisaji Oshima, Satoshi Usuda, Kazuyuki Tsunoda, Tsutomu Takeuchi
{"title":"Disease-specific autoantibody production in the lungs and salivary glands of anti-synthetase syndrome","authors":"M. Takeshita, Katsuya Suzuki, M. Nakazawa, H. Kamata, Makoto Ishii, Y. Oyamada, Hisaji Oshima, Satoshi Usuda, Kazuyuki Tsunoda, Tsutomu Takeuchi","doi":"10.3389/fimmu.2024.1265792","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1265792","url":null,"abstract":"Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody–positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases.","PeriodicalId":505785,"journal":{"name":"Frontiers in Immunology","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141348110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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