Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected family members

• Background 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.Objectives To evaluate secretory ACPA in plasma and saliva from patients with RA and FDRs.Methods 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 99th 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) >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.Results 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).

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

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