Abstract
Objective To expand in an unbiased manner our knowledge of autoantigens and autoantibodies in patients with systemic lupus erythematosus (SLE) and evaluate their associations with serological and clinical parameters.
Methods Human proteome arrays (>21,000 proteins) were screened with serum from SLE patients (n=12) and healthy controls (n=6) for IgG and IgA binding. Top hits were validated with two cohorts of SLE patients (n=49, n=46) and other rheumatic diseases by ELISA. Clinical associations of the autoantibodies were tested.
Results Ro60 was the top hit in the screen and the 10 following proteins included 2 additional known lupus autoantigens, plus 8 novel autoantigens involved in microRNA processing (AGO1, AGO2, and AGO3), ribosomes (RPLP2, OTUD5), RNA transport by the vault (MVP), and the immune proteasome (PSME3). Patient serum contained IgG reactive with these proteins and IgA against the Argonaute proteins. Using the 95th percentile of healthy donor reactivity, 5 to 43 % were positive for the novel antigens with OTUD5 and AGO1 showing the highest percentages of positivity. Autoantibodies against AGO1 proteins were more prevalent in patients with oral ulcers in a statistically significant manner. IgG autoantibodies against Argonaute proteins were also seen in other rheumatic diseases.
Conclusion We discovered new autoantigens existing in cytosolic macromolecular protein assemblies containing RNA (except the proteasome) in cells. A more comprehensive list of autoantigens will allow for a better analysis of how proteins are targeted by the autoimmune response. Future research will also reveal whether specific autoantibodies have utility in the diagnosis or management of SLE.