Arthritis autoantibodies in individuals without rheumatoid arthritis: follow-up data from a Dutch population-based cohort (Lifelines).

OBJECTIVES: To assess whether the presence of arthritis autoantibodies alongside IgG ACPA predicts clinically suspect arthralgia in ACPA-positive subjects without RA. METHODS: In the population-based Lifelines cohort (n = 40 136), 308 IgG ACPA-positive individuals without RA were present. Serum levels of IgA ACPA, IgA and IgM RF, and IgG anti-carbamylated antibodies were measured at baseline. Individuals were divided based on the Connective tissue disease Screening Questionnaire after 2 years follow-up. Antibodies to Porphyromonas gingivalis were determined at baseline and related to presence of periodontitis and joint complaints at 2 years follow-up. RESULTS: Of 308 subjects 53.6% were also seropositive for IgA ACPA, 42.2% for IgM RF, 23.7% for IgA RF and 13.6% for anti-carbamylated antibodies. We defined 75 persons with clinically suspect arthralgia at risk for RA based on CTD Screening Questionnaire at follow-up. Significantly more seropositivity for IgM RF and higher levels of IgG ACPA, IgA ACPA and IgM RF were found in clinically suspect arthralgia compared with no-clinically suspect arthralgia. In multivariate logistic regression correcting for age, gender and never smoking, positivity for three or more extra autoantibodies was significantly associated with clinically suspect arthralgia. Although levels of anti-P. gingivalis were not different between groups, they were significantly correlated to levels of both RFs, and both ACPAs in clinically suspect arthralgia. CONCLUSIONS: ACPA-positive individuals without RA who develop clinically suspect arthralgia have more and higher levels of other arthritis autoantibodies at baseline. Levels of anti-P. gingivalis are not related to self-reported periodontitis or clinically suspect arthralgia, but are correlated to arthritis autoantibodies in clinically suspect arthralgia.

Identification of autoantibody biomarkers for primary Sjögren's syndrome using protein microarrays.

Sjögren's syndrome (SS) is a chronic, progressive autoimmune disease primarily affecting women. Diagnosis of SS requires an invasive salivary gland tissue biopsy and a long delay from the start of the symptoms to final diagnosis has been frequently observed. In this study,we aim to identify salivary autoantibody biomarkers for primary SS (pSS) using a protein microarray approach. Immune-response protoarrays were used to profile saliva autoantibodies from patients with pSS (n = 514), patients with systemic lupus erythematosus(SLE, n = 513), and healthy control subjects (n = 513). We identified 24 potential autoantibody biomarkers that can discriminate patients with pSS from both patients with SLE and healthy individuals. Four saliva autoantibody biomarkers, anti-transglutaminase, anti-histone, anti-SSA, and anti-SSB, were further tested in independent pSS (n = 534), SLE (n = 534), and healthy control (n = 534) subjects and all were successfully validated with ELISA. This study has demonstrated the potential of a high-throughput protein microarray approach for the discovery of autoantibody biomarkers. The identified saliva autoantibody biomarkers may lead to a clinical tool for simple, noninvasive detection of pSS at low cost.