Extramucosal Formation and Prognostic Value of Secretory Antibodies in Rheumatoid Arthritis
© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology..
OBJECTIVE: To investigate levels and possible extramucosal formation of secretory Ig, including anti-citrullinated protein antibodies (ACPAs), in rheumatoid arthritis (RA).
METHODS: Three patient groups were studied: 1) ACPA-positive patients with musculoskeletal pain without clinical arthritis, 2) patients with recent-onset RA, and 3) patients with established RA. In baseline serum samples (groups 1 and 2) and paired synovial fluid samples (group 3), we analyzed total secretory IgA, total secretory IgM, free secretory component (SC), and SC-containing ACPA. Extramucosal formation of SC-containing ACPA was investigated by preincubating RA sera and affinity-purified ACPA with recombinant free SC.
RESULTS: Compared to healthy controls, serum levels of total secretory IgA and total secretory IgM were increased both in patients with early RA and at-risk patients (P < 0.05). Patients with early RA with elevated total secretory Ig had significantly higher disease activity during the 3-year follow-up period compared to those without increased levels. At-risk patients who developed arthritis during follow-up (39 of 82) had higher baseline total secretory IgA levels compared to those who did not (P = 0.041). In established RA, total secretory IgA and total secretory IgM levels were higher in serum than in synovial fluid (P < 0.0001), but SC-containing ACPAs adjusted for total secretory Ig concentration were higher in synovial fluid (P < 0.0001). Preincubation with recombinant free SC yielded increased SC-containing ACPA reactivity in sera as well as in affinity-purified IgA and IgM ACPA preparations.
CONCLUSION: Circulating secretory Ig are elevated before and at RA onset. In the presence of free SC, secretory Ig may form outside the mucosa, and SC-containing ACPAs are enriched in RA joints. These findings shed important new light on the mucosal connection in RA development.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
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| Enthalten in: |
Arthritis & rheumatology (Hoboken, N.J.) - 74(2022), 5 vom: 07. Mai, Seite 801-809 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Martinsson, Klara [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Citrullinated Protein Antibodies |
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| Anmerkungen: |
Date Completed 28.04.2022 Date Revised 25.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/art.42044 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM334634504 |
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| 100 | 1 | |a Martinsson, Klara |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Extramucosal Formation and Prognostic Value of Secretory Antibodies in Rheumatoid Arthritis |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. | ||
| 520 | |a OBJECTIVE: To investigate levels and possible extramucosal formation of secretory Ig, including anti-citrullinated protein antibodies (ACPAs), in rheumatoid arthritis (RA) | ||
| 520 | |a METHODS: Three patient groups were studied: 1) ACPA-positive patients with musculoskeletal pain without clinical arthritis, 2) patients with recent-onset RA, and 3) patients with established RA. In baseline serum samples (groups 1 and 2) and paired synovial fluid samples (group 3), we analyzed total secretory IgA, total secretory IgM, free secretory component (SC), and SC-containing ACPA. Extramucosal formation of SC-containing ACPA was investigated by preincubating RA sera and affinity-purified ACPA with recombinant free SC | ||
| 520 | |a RESULTS: Compared to healthy controls, serum levels of total secretory IgA and total secretory IgM were increased both in patients with early RA and at-risk patients (P < 0.05). Patients with early RA with elevated total secretory Ig had significantly higher disease activity during the 3-year follow-up period compared to those without increased levels. At-risk patients who developed arthritis during follow-up (39 of 82) had higher baseline total secretory IgA levels compared to those who did not (P = 0.041). In established RA, total secretory IgA and total secretory IgM levels were higher in serum than in synovial fluid (P < 0.0001), but SC-containing ACPAs adjusted for total secretory Ig concentration were higher in synovial fluid (P < 0.0001). Preincubation with recombinant free SC yielded increased SC-containing ACPA reactivity in sera as well as in affinity-purified IgA and IgM ACPA preparations | ||
| 520 | |a CONCLUSION: Circulating secretory Ig are elevated before and at RA onset. In the presence of free SC, secretory Ig may form outside the mucosa, and SC-containing ACPAs are enriched in RA joints. These findings shed important new light on the mucosal connection in RA development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Roos-Ljungberg, Karin |e verfasserin |4 aut | |
| 700 | 1 | |a Griazeva, Irina |e verfasserin |4 aut | |
| 700 | 1 | |a Samoylovich, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Paul, Stephane |e verfasserin |4 aut | |
| 700 | 1 | |a Rönnelid, Johan |e verfasserin |4 aut | |
| 700 | 1 | |a Weitoft, Tomas |e verfasserin |4 aut | |
| 700 | 1 | |a Wetterö, Jonas |e verfasserin |4 aut | |
| 700 | 1 | |a Kastbom, Alf |e verfasserin |4 aut | |
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