Multi-Autoantibody Testing Identifies Expansion of Reactivity to Targeted Antigens Before a Diagnosis of Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) has a "pre-RA" period in which multiple autoantibodies, including antibodies to citrullinated (cit) proteins (ACPA), rheumatoid factor (RF), anti-peptidyl arginine deiminase (anti-PAD), among others, have been described; however, few studies have tested all autoantibodies in a single pre-RA cohort. This study aims to evaluate the prevalence of multiple autoantibodies in pre-RA and potentially identify an autoantibody profile in pre-RA that indicates imminent onset of clinical RA. METHODS: We evaluated 148 individuals with two pre- and one post-RA diagnosis samples available from the Department of Defense Serum Repository and matched controls. Samples were tested for immuglobulin (Ig) G anti-cyclic cit peptide-3 (anti-CCP3), five ACPA fine specificities, five anti-PAD isoforms, as well as RF IgA and RF IgM using commercial platforms; cutoffs were determined using levels present in <1% of controls. RESULTS: Positivity of anti-CCP3, RF IgA and RF IgM, anti-PAD1, anti-cit-vimentin 2, anti-cit-fibrinogen, and anti-cit-histone 1 increased over time in pre-RA, although anti-PAD and ACPA fine specificities were predominately present within anti-CCP3-positive individuals. Within anti-CCP3-positive samples from the pre-RA period, positivity for RFs as well as anti-PAD and ACPA fine specificities classified samples as being closer to the time of RA diagnosis. CONCLUSION: Multiple autoantibodies are present in pre-RA and increase in positivity as the time of RA diagnosis approaches. These results confirm previous findings predicting imminent RA and provide a pathway using commercial-grade assays to assess the risk for and timing of development of clinical RA.

Performance Characteristics of Different Anti-Double-Stranded DNA Antibody Assays in the Monitoring of Systemic Lupus Erythematosus.

OBJECTIVE: We sought to evaluate different anti-double-stranded DNA assays for their performance characteristics in monitoring disease activity fluctuations in systemic lupus erythematosus (SLE). METHODS: 36 active SLE patients were followed monthly. At each study visit (total n = 371), blood was collected and disease activity was scored using the SELENA-SLEDAI (excluding anti-dsDNA or complement components) and by a physician's global assessment (PGA). Four anti-dsDNA tests were compared. Linear mixed-effects models with random intercept and fixed slopes were used to evaluate the relationship between the longitudinal fluctuations of disease activity and anti-dsDNA titers. RESULTS: At enrollment, positivity for QUANTA Lite and high-avidity anti-dsDNA assay was both 64% and significantly lower than anti-dsDNA positivity by QUANTA Flash (83%) and CLIFT (96%). Linear mixed-effects modeling indicated that the change in clinical SELENA-SLEDAI scores was associated with the titers of all anti-dsDNA with QUANTA Flash yielding the highest marginal R2 (0.15; p < 0.01). QUANTA Flash was the only anti-dsDNA assay significantly associated with the change in PGA (marginal R2 = 0.05; p < 0.01). CONCLUSION: These data indicate that anti-dsDNA antibodies determined by QUANTA Flash have a value in monitoring SLE disease activity.