Serum autoantibody profiling in systemic lupus erythematosus reveals associations with low disease activity and remission

Abstract

Knowledge of autoantibody specificities and their clinical associations in systemic lupus erythematosus (SLE) is largely limited to panels testing a finite number of autoantibodies. We aimed to explore high-plex serum autoantibody profiles in SLE and examine associations with socio-demographics, phenotypes and outcomes using an unbiased approach. In this exploratory, biomarker-discovery study, 1,613 serum IgG autoantibodies were quantified using an i-Ome® Discovery Protein Array in 60 patients with SLE. The array was customised to detect antibodies against three interferons. Autoantibody clusters were defined using unsupervised clustering and associations between clusters and clinical features were assessed using multinomial logistic regression. Associations between individual autoantibodies and clinical features were assessed using regression models and supervised learning. Four patient clusters were identified; Cluster 4, characterised by anti-La and anti-Ro60 autoantibodies, included patients significantly more likely to be of Asian ethnicity and with higher ESR levels than those in Cluster 1. In analysis of individual autoantibody specificities, anti-LRR binding FLII-interacting protein 2 (anti-LRRFIP2) was associated with remission and lupus low disease activity state (LLDAS). Anti-gephyrin (GPHN) was associated with CNS lupus. Anti-adaptor protein-2 associated kinase 1 (anti-AAK1), anti-ribosomal protein S6 kinase B1 (anti-RPS6KB1) and anti-ribosomal protein S6 kinase B2 (anti-RSP6KB2) were negatively associated with mucocutaneous lupus. Unsupervised clustering of autoantibody profiles revealed a patient subset with anti-La and anti-Ro60 profiles, associated with Asian ethnicity and higher ESR. Anti-LRRFIP2 was associated with remission and LLDAS, and anti-GPHN, previously described in autoimmune CNS disease, was associated with CNS lupus. While these exploratory associations warrant validation in larger independent cohorts, the identification of biomarker candidates highlights the potential value of comprehensive IgG autoantibody profiling for biomarker discovery in SLE.