Guillem Montamat, Claire E Meehan, Hannah F Bradford, Reşit Yıldırım, Francisca Guimarães, Marina Johnson, David Goldblatt, David A Isenberg, Claudia Mauri
{"title":"SLE患者对SARS-CoV-2疫苗应答降低与免疫球蛋白类开关重组受损有关。","authors":"Guillem Montamat, Claire E Meehan, Hannah F Bradford, Reşit Yıldırım, Francisca Guimarães, Marina Johnson, David Goldblatt, David A Isenberg, Claudia Mauri","doi":"10.1093/cei/uxae119","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Systemic lupus erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine antigens, and boosters number, is important to avoid unnecessarily prolonged isolation of immunocompromised individuals. We assessed humoral and antigen-specific B-cell subset responses, including changes in isotype switching, prior to and after several doses of SARS-CoV-2 vaccines.</p><p><strong>Methods: </strong>Blood samples were obtained prior to and after SARS-CoV-2 vaccination from cross-sectional and longitudinal cohorts of previously uninfected patients with SLE (n = 93). Healthy participants receiving SARS-CoV-2 vaccines were recruited as controls (n = 135). We measured serum antibody titres, their neutralizing capacity, and vaccine-specific memory B-cell subsets.</p><p><strong>Results: </strong>Impaired IgG, IgA, and neutralizing responses against the original and various SARS-CoV-2 variants were observed following two doses of vaccine in SLE patients. Follow-up booster doses increased humoral responses compared to baseline, but they remained lower, with poorer neutralisation capacity against most strains, compared to healthy individuals after three or more doses. Analysis of memory B-cell subsets in SLE patients revealed an increase of SARS-CoV-2-specific isotype unswitched IgM+ over SARS-CoV-2-specific isotype switched IgG+/IgA+ memory B-cells compared to healthy individuals. Culturing healthy naive B-cells with high levels of IFNα, a hallmark of SLE pathogenesis, prevented B-cells from switching to IgG under IgG-polarizing conditions.</p><p><strong>Conclusion: </strong>SLE patients' protection against SARS-CoV-2 is overall impaired compared to healthy individuals and is associated with a class switch defect possibly due to chronic exposure of B-cells to IFNα.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773804/pdf/","citationCount":"0","resultStr":"{\"title\":\"Reduced response to SARS-CoV-2 vaccination is associated with impaired immunoglobulin class switch recombination in SLE patients.\",\"authors\":\"Guillem Montamat, Claire E Meehan, Hannah F Bradford, Reşit Yıldırım, Francisca Guimarães, Marina Johnson, David Goldblatt, David A Isenberg, Claudia Mauri\",\"doi\":\"10.1093/cei/uxae119\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Systemic lupus erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine antigens, and boosters number, is important to avoid unnecessarily prolonged isolation of immunocompromised individuals. We assessed humoral and antigen-specific B-cell subset responses, including changes in isotype switching, prior to and after several doses of SARS-CoV-2 vaccines.</p><p><strong>Methods: </strong>Blood samples were obtained prior to and after SARS-CoV-2 vaccination from cross-sectional and longitudinal cohorts of previously uninfected patients with SLE (n = 93). Healthy participants receiving SARS-CoV-2 vaccines were recruited as controls (n = 135). We measured serum antibody titres, their neutralizing capacity, and vaccine-specific memory B-cell subsets.</p><p><strong>Results: </strong>Impaired IgG, IgA, and neutralizing responses against the original and various SARS-CoV-2 variants were observed following two doses of vaccine in SLE patients. Follow-up booster doses increased humoral responses compared to baseline, but they remained lower, with poorer neutralisation capacity against most strains, compared to healthy individuals after three or more doses. Analysis of memory B-cell subsets in SLE patients revealed an increase of SARS-CoV-2-specific isotype unswitched IgM+ over SARS-CoV-2-specific isotype switched IgG+/IgA+ memory B-cells compared to healthy individuals. Culturing healthy naive B-cells with high levels of IFNα, a hallmark of SLE pathogenesis, prevented B-cells from switching to IgG under IgG-polarizing conditions.</p><p><strong>Conclusion: </strong>SLE patients' protection against SARS-CoV-2 is overall impaired compared to healthy individuals and is associated with a class switch defect possibly due to chronic exposure of B-cells to IFNα.</p>\",\"PeriodicalId\":10268,\"journal\":{\"name\":\"Clinical and experimental immunology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-01-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773804/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and experimental immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/cei/uxae119\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and experimental immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/cei/uxae119","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Reduced response to SARS-CoV-2 vaccination is associated with impaired immunoglobulin class switch recombination in SLE patients.
Introduction: Systemic lupus erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine antigens, and boosters number, is important to avoid unnecessarily prolonged isolation of immunocompromised individuals. We assessed humoral and antigen-specific B-cell subset responses, including changes in isotype switching, prior to and after several doses of SARS-CoV-2 vaccines.
Methods: Blood samples were obtained prior to and after SARS-CoV-2 vaccination from cross-sectional and longitudinal cohorts of previously uninfected patients with SLE (n = 93). Healthy participants receiving SARS-CoV-2 vaccines were recruited as controls (n = 135). We measured serum antibody titres, their neutralizing capacity, and vaccine-specific memory B-cell subsets.
Results: Impaired IgG, IgA, and neutralizing responses against the original and various SARS-CoV-2 variants were observed following two doses of vaccine in SLE patients. Follow-up booster doses increased humoral responses compared to baseline, but they remained lower, with poorer neutralisation capacity against most strains, compared to healthy individuals after three or more doses. Analysis of memory B-cell subsets in SLE patients revealed an increase of SARS-CoV-2-specific isotype unswitched IgM+ over SARS-CoV-2-specific isotype switched IgG+/IgA+ memory B-cells compared to healthy individuals. Culturing healthy naive B-cells with high levels of IFNα, a hallmark of SLE pathogenesis, prevented B-cells from switching to IgG under IgG-polarizing conditions.
Conclusion: SLE patients' protection against SARS-CoV-2 is overall impaired compared to healthy individuals and is associated with a class switch defect possibly due to chronic exposure of B-cells to IFNα.
期刊介绍：
Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice.
The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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