Extramucosal Formation and Prognostic Value of Secretory Antibodies in Rheumatoid Arthritis.
Arthritis Rheumatol
; 74(5): 801-809, 2022 05.
Article
in En
| MEDLINE
| ID: mdl-34927393
ABSTRACT
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.
Full text:
1
Database:
MEDLINE
Main subject:
Arthritis, Rheumatoid
/
Anti-Citrullinated Protein Antibodies
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Arthritis Rheumatol
Year:
2022
Type:
Article
Affiliation country:
Sweden