SAT0067 SECRETORY ANTIBODIES TO CITRULLINATED PEPTIDES IN PLASMA AND SALIVA FROM RHEUMATOID ARTHRITIS PATIENTS AND THEIR UNAFFECTED FAMILY MEMBERS
Authors: Anna Svärd, Karin Roos Ljungberg, Mikael Brink, Alf Kastbom, Solbritt Rantapää Dahlqvist
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Mucosal involvement in early phases of rheumatoid arthritis (RA) pathophysiology has emerged as an attractive hypothesis, supported by several findings. Elevated levels of antibodies against citrullinated peptides/proteins (ACPA) can be found during a long pre-symptomatic period, preceding manifest arthritis. Secretory antibodies are produced at mucosal surfaces, but can also be detected in the circulation. Secretory ACPA in plasma has been demonstrated in patients with RA (1). First-degree relatives (FDRs) of patients with RA can be regarded as potential pre-RA patients or at-risk individuals. In a previous study, a higher prevalence of ACPA was found in FDRs than in healthy controls (2), with IgA-ACPA being more common than IgG-ACPA. We hypothesized that formation of secretory ACPA is an early step in RA development, preceding the occurrence of regular non-secretory ACPA, and consequently secretory ACPA would be prevalent in a large proportion of FDRs. <h3>Objectives</h3> To evaluate secretory ACPA in plasma and saliva from patients with RA and FDRs. <h3>Methods</h3> We analyzed secretory antibodies to 2nd generation cyclic citrullinated peptides (anti-CCP) in plasma from 194 patients with RA and 191 FDRs unaffected by RA and salivary samples from 25 RA patients, 21 first-degree relatives and 11 controls. In plasma, cutoff for secretory ACPA was set at the 99<sup>th</sup> percentile of healthy blood donors. In saliva, a positive test was defined as a difference between optical density values for IgA anti-CCP and IgA anti-cyclic arginine peptide (delta OD value) &gt;2 SD above the mean delta OD value of the controls. Mann-Whitney U test was used for continuous variables and Pearson Chi-square for categorical variables. <h3>Results</h3> Secretory ACPA occurred in 37 (19.1%) of RA patients but only in 2 (1%) of FDRs (table 1). Salivary IgA ACPA was found in 3/25 (12%) of patients with RA, but not in any of the 21 FDRs. 27% of FDRs were positive for regular non-secretory IgA ACPA in plasma, and out of them, only 2 individuals (5%) were positive for secretory ACPA in plasma. Among FDRs negative for regular ACPAs, no one was positive for secretory ACPA. Secretory ACPA had the highest PPV for identifying patients, while IgG ACPA had the highest negative predictive value (table 2). <h3>Conclusion</h3> Secretory ACPA in plasma and saliva was rare in FDRs. Circulating secretory ACPA had the highest PPV of the RA-related antibodies tested to identify RA in these families. This implies that mucosal production of ACPA is not common in an at-risk population, but may be important in the transition from increased risk to actual RA disease. <h3>References</h3> [1] Roos K, et al. Arthritis Res Ther. 2016;18(1):119. [2] Young KA, et al. Arthritis Rheum. 2013;65(8):1995-2004. <h3>Disclosure of Interests</h3> Anna Svärd: None declared, Karin Roos Ljungberg: None declared, Mikael Brink Shareholder of: Owns shares in Bristol-Myers Squibb Co, Alf Kastbom Consultant for: Roche and Pfizer, Employee of: Sanofi, Speakers bureau: UCB and BMS, Solbritt Rantapää Dahlqvist Consultant for: Member of the advisory board, Lipum AB, Umeå, Sweden.