PT  - JOURNAL ARTICLE
AU  - Azita Sohrabian
AU  - Linda Mathsson-Alm
AU  - Monika Hansson
AU  - Ann Knight
AU  - Jörgen Lysholm
AU  - Martin Cornillet
AU  - Karl Skriner
AU  - Guy Serre
AU  - Anders Larsson
AU  - Tomas Weitoft
AU  - Johan Rönnelid
TI  - Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis
AID  - 10.1136/annrheumdis-2017-212627
DP  - 2018 Jun 08
TA  - Annals of the Rheumatic Diseases
PG  - annrheumdis-2017-212627
4099  - http://ard.bmj.com/content/early/2018/06/07/annrheumdis-2017-212627.short
4100  - http://ard.bmj.com/content/early/2018/06/07/annrheumdis-2017-212627.full
AB  - Introduction Individual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.Methods We have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.Results The majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.Conclusions Our data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.