Autoantibodies against adenosine deaminase acting on RNA1 (ADAR1) in patients with systemic lupus erythematosus: its relationship to clinical features and other autoantibodies
Sara Komatsu, Kazuhiro Kurasawa, Aya Shimizu, Tomoka Hiyama, Azusa Kikuchi, Yuhi Yoshida, Anna Hasegawa, Tomoyuki Miyao, Ayae Tanaka, Satoko Arai, Reika Maezawa, Masafumi Arima, Kei IkedaAbstract
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.