Disease-specific autoantibody production in the lungs and salivary glands of anti-synthetase syndrome
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 investigat...
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| Published in | FRONTIERS IN IMMUNOLOGY Vol. 15; p. 1265792 |
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| 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. |
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| AbstractList | 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. 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.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. |
| Author | Masaru Takeshita Hirofumi Kamata Satoshi Usuda Makoto Ishii Tsutomu Takeuchi Hisaji Oshima Kazuyuki Tsunoda Katsuya Suzuki Maho Nakazawa Yoshitaka Oyamada |
| AuthorAffiliation | 8 Saitama Medical University , Saitama , Japan 5 Department of Respiratory Medicine, National Tokyo Medical Center , Meguro , Japan 2 Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet , Stockholm , Sweden 6 Department of Connective Tissue Diseases, National Tokyo Medical Center , Meguro , Japan 3 Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine , Shinjuku , Japan 7 Department of Dentistry and Oral Surgery, Keio University School of Medicine , Shinjuku , Japan 1 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Shinjuku , Japan 4 Division of Respiratory Medicine, Nagoya University Graduate School of Medicine , Nagoya , Japan |
| AuthorAffiliation_xml | – name: 3 Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine , Shinjuku , Japan – name: 8 Saitama Medical University , Saitama , Japan – name: 7 Department of Dentistry and Oral Surgery, Keio University School of Medicine , Shinjuku , Japan – name: 6 Department of Connective Tissue Diseases, National Tokyo Medical Center , Meguro , Japan – name: 5 Department of Respiratory Medicine, National Tokyo Medical Center , Meguro , Japan – name: 1 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine , Shinjuku , Japan – name: 4 Division of Respiratory Medicine, Nagoya University Graduate School of Medicine , Nagoya , Japan – name: 2 Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet , Stockholm , Sweden |
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| Cites_doi | 10.1080/08916930600622884 10.1136/annrheumdis-2017–211468 10.1136/annrheumdis-2019–215862 10.1172/JCI114461 10.1016/j.jaut.2019.04.001 10.1136/annrheumdis-2018–215004 10.1073/pnas.87.24.9933 10.1007/s11926–015-0532–1 10.1097/BOR.0000000000000555 10.1016/j.jaut.2021.102661 10.4049/jimmunol.169.12.7127 10.1378/chest.10–0180 10.55563/clinexprheumatol/bjb2gf 10.1080/19420862.2020.1836718 10.1111/1756–185X.13439 10.1002/art.41075 10.2169/internalmedicine.49.2889 10.1111/1346–8138.15049 10.1016/s0167–5699(99)01458–9 10.1038/nrrheum.2018.56 10.1148/radiol.2322031223 10.1002/art.39859 10.3389/fimmu.2019.00444 10.1016/j.cca.2014.01.005 10.1038/nprot.2014.006 10.1097/md.0000000000015578 10.1016/j.celrep.2021.109604 10.1136/annrheumdis-2022-eular.1980 10.1002/art.41964 10.1016/j.berh.2020.101503 10.1016/s0140–6736(86)92429–3 10.1002/art.22790 10.1002/art.41554 10.1016/j.autrev.2021.103013 10.3109/14397595.2015.1091155 |
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| Keywords | idiopathic inflammatory myopathy salivary gland anti-Ro52 antibody anti-synthetase syndrome autoantibody anti-aminoacyl-tRNA synthetase antibody |
| Language | English |
| License | Copyright © 2024 Takeshita, Suzuki, Nakazawa, Kamata, Ishii, Oyamada, Oshima, Usuda, Tsunoda and Takeuchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Snippet | Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have... |
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| SubjectTerms | Adult Aged anti-aminoacyl-tRNA synthetase antibody anti-Ro52 antibody anti-synthetase syndrome Antibodies, Antinuclear - immunology Autoantibodies - immunology autoantibody Autoantigens - immunology B-Lymphocytes - immunology Bronchoalveolar Lavage Fluid - immunology Female Humans idiopathic inflammatory myopathy Immunologic diseases. Allergy Immunology Lung - immunology Lung - pathology Lung Diseases, Interstitial - immunology Male Middle Aged Myositis - immunology RC581-607 salivary gland Salivary Glands - immunology Salivary Glands - pathology |
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| Title | Disease-specific autoantibody production in the lungs and salivary glands of anti-synthetase syndrome |
| URI | https://cir.nii.ac.jp/crid/1870303266603258624 https://www.ncbi.nlm.nih.gov/pubmed/38938569 https://www.proquest.com/docview/3073233350 https://pubmed.ncbi.nlm.nih.gov/PMC11208671 http://kipublications.ki.se/Default.aspx?queryparsed=id https://doaj.org/article/d7f67e22fa9f430da443f477468e3e06 |
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