Cargando…
In rheumatoid arthritis inflamed joints share dominant patient-specific B-cell clones
BACKGROUND: In patients with rheumatoid arthritis (RA) different joints were shown to share the same dominant T-cell clones, suggesting shared characteristics of the inflammatory process and indicating that strategies to selectively target the antigen receptor might be feasible. Since T- and B-lymph...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363889/ https://www.ncbi.nlm.nih.gov/pubmed/35967291 http://dx.doi.org/10.3389/fimmu.2022.915687 |
_version_ | 1784765033456074752 |
---|---|
author | Musters, Anne Balzaretti, Giulia van Schaik, Barbera D. C. Jongejan, Aldo van der Weele, Linda Tas, Sander W. van Kampen, Antoine H. C. de Vries, Niek |
author_facet | Musters, Anne Balzaretti, Giulia van Schaik, Barbera D. C. Jongejan, Aldo van der Weele, Linda Tas, Sander W. van Kampen, Antoine H. C. de Vries, Niek |
author_sort | Musters, Anne |
collection | PubMed |
description | BACKGROUND: In patients with rheumatoid arthritis (RA) different joints were shown to share the same dominant T-cell clones, suggesting shared characteristics of the inflammatory process and indicating that strategies to selectively target the antigen receptor might be feasible. Since T- and B-lymphocytes closely interact in adaptive responses, we analysed to what extent different joints also share dominant B-cell clones. METHODS: In 11 RA patients, quantitative B-cell receptor (BCR) repertoire analysis was performed in simultaneously obtained samples from inflamed synovial tissue (ST) from distinct locations within one joint, from multiple joints, from synovial fluid (SF) and peripheral blood (PB). RESULTS: ST biopsies from different locations in the same joint showed clear overlap in the top-25 dominant BCR clones (16.7%, SD 12.5), in the same range as the overlap between ST and SF in the same joint (8.0%, SD 8.8) and the overlap between ST-ST between different joints (9.1%, SD 8.2), but clearly higher than the overlap between ST and PB (1.7%, SD 2.4; p<0.05) and SF and PB (2.7%, SD 4.1; p<0.05). Interestingly, these figures were substantially lower than the overlap observed in previous T-cell clonality studies. CONCLUSIONS: We conclude that in RA BCR clonal responses may be more localized than TCR clonal responses, pointing to antigen-selective influx, proliferation and/or maturation of B-cells. B lineage cells in the SF may adequately represent the dominant BCR clones of the ST, which is in contrast to T-cells. Collectively, the presence of shared B- and especially T-cells in different joints from the same patient suggests that approaches might be feasible that aim to develop antigen-receptor specific targeting of lymphocyte clones in RA as an alternative to more generalized immunosuppressive strategies. |
format | Online Article Text |
id | pubmed-9363889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93638892022-08-11 In rheumatoid arthritis inflamed joints share dominant patient-specific B-cell clones Musters, Anne Balzaretti, Giulia van Schaik, Barbera D. C. Jongejan, Aldo van der Weele, Linda Tas, Sander W. van Kampen, Antoine H. C. de Vries, Niek Front Immunol Immunology BACKGROUND: In patients with rheumatoid arthritis (RA) different joints were shown to share the same dominant T-cell clones, suggesting shared characteristics of the inflammatory process and indicating that strategies to selectively target the antigen receptor might be feasible. Since T- and B-lymphocytes closely interact in adaptive responses, we analysed to what extent different joints also share dominant B-cell clones. METHODS: In 11 RA patients, quantitative B-cell receptor (BCR) repertoire analysis was performed in simultaneously obtained samples from inflamed synovial tissue (ST) from distinct locations within one joint, from multiple joints, from synovial fluid (SF) and peripheral blood (PB). RESULTS: ST biopsies from different locations in the same joint showed clear overlap in the top-25 dominant BCR clones (16.7%, SD 12.5), in the same range as the overlap between ST and SF in the same joint (8.0%, SD 8.8) and the overlap between ST-ST between different joints (9.1%, SD 8.2), but clearly higher than the overlap between ST and PB (1.7%, SD 2.4; p<0.05) and SF and PB (2.7%, SD 4.1; p<0.05). Interestingly, these figures were substantially lower than the overlap observed in previous T-cell clonality studies. CONCLUSIONS: We conclude that in RA BCR clonal responses may be more localized than TCR clonal responses, pointing to antigen-selective influx, proliferation and/or maturation of B-cells. B lineage cells in the SF may adequately represent the dominant BCR clones of the ST, which is in contrast to T-cells. Collectively, the presence of shared B- and especially T-cells in different joints from the same patient suggests that approaches might be feasible that aim to develop antigen-receptor specific targeting of lymphocyte clones in RA as an alternative to more generalized immunosuppressive strategies. Frontiers Media S.A. 2022-07-27 /pmc/articles/PMC9363889/ /pubmed/35967291 http://dx.doi.org/10.3389/fimmu.2022.915687 Text en Copyright © 2022 Musters, Balzaretti, van Schaik, Jongejan, van der Weele, Tas, van Kampen and de Vries https://creativecommons.org/licenses/by/4.0/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. |
spellingShingle | Immunology Musters, Anne Balzaretti, Giulia van Schaik, Barbera D. C. Jongejan, Aldo van der Weele, Linda Tas, Sander W. van Kampen, Antoine H. C. de Vries, Niek In rheumatoid arthritis inflamed joints share dominant patient-specific B-cell clones |
title | In rheumatoid arthritis inflamed joints share dominant patient-specific B-cell clones |
title_full | In rheumatoid arthritis inflamed joints share dominant patient-specific B-cell clones |
title_fullStr | In rheumatoid arthritis inflamed joints share dominant patient-specific B-cell clones |
title_full_unstemmed | In rheumatoid arthritis inflamed joints share dominant patient-specific B-cell clones |
title_short | In rheumatoid arthritis inflamed joints share dominant patient-specific B-cell clones |
title_sort | in rheumatoid arthritis inflamed joints share dominant patient-specific b-cell clones |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363889/ https://www.ncbi.nlm.nih.gov/pubmed/35967291 http://dx.doi.org/10.3389/fimmu.2022.915687 |
work_keys_str_mv | AT mustersanne inrheumatoidarthritisinflamedjointssharedominantpatientspecificbcellclones AT balzarettigiulia inrheumatoidarthritisinflamedjointssharedominantpatientspecificbcellclones AT vanschaikbarberadc inrheumatoidarthritisinflamedjointssharedominantpatientspecificbcellclones AT jongejanaldo inrheumatoidarthritisinflamedjointssharedominantpatientspecificbcellclones AT vanderweelelinda inrheumatoidarthritisinflamedjointssharedominantpatientspecificbcellclones AT tassanderw inrheumatoidarthritisinflamedjointssharedominantpatientspecificbcellclones AT vankampenantoinehc inrheumatoidarthritisinflamedjointssharedominantpatientspecificbcellclones AT devriesniek inrheumatoidarthritisinflamedjointssharedominantpatientspecificbcellclones |