Autoantibodies against adenosine deaminase acting on RNA1 (ADAR1) in patients with systemic lupus erythematosus: its relationship to clinical features and other autoantibodies.

Abstract

Objectives: Adenosine deaminase acting on RNA 1 (ADAR1) is an interferon (IFN)-inducible RNA-editing enzyme involved in the regulation of IFN signaling pathways. Although increased ADAR1 expression has been reported in systemic lupus erythematosus (SLE), the presence and clinical significance of anti-ADAR1 antibodies remain unclear.

Methods: Serum samples from patients with SLE, idiopathic inflammatory myopathy (IIM), and rheumatoid arthritis (RA) were analyzed. Anti-ADAR1 antibodies were quantified using a newly developed ELISA, and specificity was confirmed by inhibition testing. Clinical and serological features were compared between antibody-positive and -negative patients. Hierarchical clustering and logistic regression analyses were performed to identify patient subsets and associated clinical features.

Results: Anti-ADAR1 antibodies were detected in 38 of 76 patients with SLE (50.0%), 29 of 130 with IIM (22.3%), and 2 of 22 with RA (9.0%). In SLE, patients with anti-ADAR1 antibodies more frequently exhibited pericarditis, myocarditis, splenomegaly, elevated immunoglobulin G levels, and positivity for anti-U1RNP, anti-Sm, and anti-SSA antibodies. Cluster analysis identified three subgroups, with anti-ADAR1 antibodies enriched in a subset characterized by co-occurrence of autoantibodies against RNA-binding proteins. Exploratory analyses suggested that some clinical features showed different patterns of association with anti-ADAR1 antibody positivity and Cluster 3 membership.

Conclusions: Anti-ADAR1 antibodies are frequently detected in SLE and IIM, but are rare in RA. These antibodies are enriched in a subset of SLE cases characterized by coordinated production of antibodies against RNA-binding proteins within an IFN-related immunological context. These findings suggest that anti-ADAR1 antibodies may contribute to immunological stratification of SLE.