Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected first-degree relatives

A Svärd, K Roos Ljungberg, M Brink, K Martinsson, C Sjöwall, S Rantapää Dahlqvist, A Kastbom, A Svärd, K Roos Ljungberg, M Brink, K Martinsson, C Sjöwall, S Rantapää Dahlqvist, A Kastbom

Abstract

The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.

Keywords: ACPA; mucosa; relatives; rheumatoid arthritis; secretory immunoglobulin.

Conflict of interest statement

There are no conflicts of interest to declare.

© 2019 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Figures

Figure 1
Figure 1
Frequencies of rheumatoid factors [immunoglobulin (Ig)M and IgA] and anti‐citrullinated protein antibodies (IgG and IgA) in first‐degree relatives (FDR; n = 157) and patients with rheumatoid arthritis (RA; n = 163), secretory ACPA in plasma (n = 191 and n = 194, respectively) and IgA‐ACPA in salivary samples (n = 21 and n = 25, respectively). Error bars represent 95% confidence intervals.
Figure 2
Figure 2
Adjusted odds ratios for having rheumatoid arthritis, based on antibody positivity, with first‐degree relatives as reference. Results from regression analyses, one separate analysis for each antibody.

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