Serological abnormalities that predict progression to systemic autoimmune rheumatic diseases in antinuclear antibody positive individuals.

Objective We investigated the auto-antibody (auto-Ab) profiles in anti-nuclear antibody-positive (ANA+) individuals lacking Systemic Autoimmune Rheumatic Disease (SARD) and early SARD patients, to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next two years in ANA+ individuals. Methods Using custom antigen (Ag) microarrays, 144 IgM and IgG auto-Abs were surveyed in 84 asymptomatic and 123 symptomatic (48 undifferentiated connective tissue disease (UCTD) and 75 SARD patients) ANA+ individuals. Auto-Ab were compared in ANA+ individuals lacking a SARD diagnosis with ≥ 2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset. Results We show that ANA+ individuals have auto-Ab to many self-Ag that are not being captured by current screening techniques and very high levels of these auto-Abs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more auto-Ags than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of auto-Ab. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years follow-up the levels of auto-Ab remained remarkably stable regardless of whether individuals progressed or not. Conclusion Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of auto-Ab testing.