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Natural autoimmunity in oligoarticular juvenile idiopathic arthritis
BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligo-JIA) is considered as an antigen-driven lymphocyte-mediated autoimmune disease. Natural antibodies (NAbs) are pre-immune antibodies produced in the absence of exogenous antigen stimulation, participating in both, innate and adaptive imm...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155367/ https://www.ncbi.nlm.nih.gov/pubmed/37138302 http://dx.doi.org/10.1186/s12969-023-00823-w |
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author | Tsitsami, Elena Sarrigeorgiou, Ioannis Tsinti, Maria Rouka, Erasmia C. Zarogiannis, Sotirios G. Lymberi, Peggy |
author_facet | Tsitsami, Elena Sarrigeorgiou, Ioannis Tsinti, Maria Rouka, Erasmia C. Zarogiannis, Sotirios G. Lymberi, Peggy |
author_sort | Tsitsami, Elena |
collection | PubMed |
description | BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligo-JIA) is considered as an antigen-driven lymphocyte-mediated autoimmune disease. Natural antibodies (NAbs) are pre-immune antibodies produced in the absence of exogenous antigen stimulation, participating in both, innate and adaptive immunity. Considering their major immunoregulatory role in homeostasis and autoimmune pathogenesis, we designed this study to further elucidate their role in oligo-JIA pathogenesis. METHODS: Seventy children with persistent oligo-JIA and 20 healthy matched controls were enrolled in the study. Serum IgM and IgA antibodies against human G-actin, human IgG F(ab΄)2 fragments and the hapten TriNitroPhenol (TNP) as well as the total concentration of serum IgM and IgA were measured by in-house enzyme-immunoassays. Kolmogorov–Smirnov normality test, Kruskal–Wallis H and Mann–Whitney tests were used to assess data distribution, and significant differences of non-parametric data between groups of the study. Backward regression analysis was used to analyze the effect of multiple factors (age, gender, disease activity, anti-nuclear antibody positivity, presence of uveitis) on continuous dependent variables (activities and activity/ concentration ratios of IgM and IgA NAbs). RESULTS: The ratios of IgA anti-TNP, anti-actin and anti-F(ab΄)(2) levels to total serum IgA concentration were found to be significantly increased in patients with oligo-JIA compared to healthy subjects. Significantly elevated levels of IgM anti-TNP antibodies were also found in children with inactive oligo-JIA compared to those of children with active disease and of healthy controls. In the presence of anterior uveitis, IgM anti-TNP levels were significantly higher than in patients without uveitis or in healthy controls. Backward regression analysis revealed that the disease activity and the presence of anterior uveitis independently affect IgM anti-TNP levels. CONCLUSUIONS: Our findings are in accordance with the hypothesis that NAbs contribute to the pathogenesis of autoimmune diseases and provide additional evidence that disturbances in natural autoimmunity may contribute to the as yet unclarified pathogenesis of oligo-JIA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12969-023-00823-w. |
format | Online Article Text |
id | pubmed-10155367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101553672023-05-04 Natural autoimmunity in oligoarticular juvenile idiopathic arthritis Tsitsami, Elena Sarrigeorgiou, Ioannis Tsinti, Maria Rouka, Erasmia C. Zarogiannis, Sotirios G. Lymberi, Peggy Pediatr Rheumatol Online J Research Article BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligo-JIA) is considered as an antigen-driven lymphocyte-mediated autoimmune disease. Natural antibodies (NAbs) are pre-immune antibodies produced in the absence of exogenous antigen stimulation, participating in both, innate and adaptive immunity. Considering their major immunoregulatory role in homeostasis and autoimmune pathogenesis, we designed this study to further elucidate their role in oligo-JIA pathogenesis. METHODS: Seventy children with persistent oligo-JIA and 20 healthy matched controls were enrolled in the study. Serum IgM and IgA antibodies against human G-actin, human IgG F(ab΄)2 fragments and the hapten TriNitroPhenol (TNP) as well as the total concentration of serum IgM and IgA were measured by in-house enzyme-immunoassays. Kolmogorov–Smirnov normality test, Kruskal–Wallis H and Mann–Whitney tests were used to assess data distribution, and significant differences of non-parametric data between groups of the study. Backward regression analysis was used to analyze the effect of multiple factors (age, gender, disease activity, anti-nuclear antibody positivity, presence of uveitis) on continuous dependent variables (activities and activity/ concentration ratios of IgM and IgA NAbs). RESULTS: The ratios of IgA anti-TNP, anti-actin and anti-F(ab΄)(2) levels to total serum IgA concentration were found to be significantly increased in patients with oligo-JIA compared to healthy subjects. Significantly elevated levels of IgM anti-TNP antibodies were also found in children with inactive oligo-JIA compared to those of children with active disease and of healthy controls. In the presence of anterior uveitis, IgM anti-TNP levels were significantly higher than in patients without uveitis or in healthy controls. Backward regression analysis revealed that the disease activity and the presence of anterior uveitis independently affect IgM anti-TNP levels. CONCLUSUIONS: Our findings are in accordance with the hypothesis that NAbs contribute to the pathogenesis of autoimmune diseases and provide additional evidence that disturbances in natural autoimmunity may contribute to the as yet unclarified pathogenesis of oligo-JIA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12969-023-00823-w. BioMed Central 2023-05-03 /pmc/articles/PMC10155367/ /pubmed/37138302 http://dx.doi.org/10.1186/s12969-023-00823-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Tsitsami, Elena Sarrigeorgiou, Ioannis Tsinti, Maria Rouka, Erasmia C. Zarogiannis, Sotirios G. Lymberi, Peggy Natural autoimmunity in oligoarticular juvenile idiopathic arthritis |
title | Natural autoimmunity in oligoarticular juvenile idiopathic arthritis |
title_full | Natural autoimmunity in oligoarticular juvenile idiopathic arthritis |
title_fullStr | Natural autoimmunity in oligoarticular juvenile idiopathic arthritis |
title_full_unstemmed | Natural autoimmunity in oligoarticular juvenile idiopathic arthritis |
title_short | Natural autoimmunity in oligoarticular juvenile idiopathic arthritis |
title_sort | natural autoimmunity in oligoarticular juvenile idiopathic arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155367/ https://www.ncbi.nlm.nih.gov/pubmed/37138302 http://dx.doi.org/10.1186/s12969-023-00823-w |
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