The following is a summary of “Argonaute, Vault, and Ribosomal Proteins Targeted by Autoantibodies in Systemic Lupus Erythematosus,” published in the September 2023 issue of Rheumatology by Moadab et al.
Researchers performed a retrospective study to expand the understanding of autoantigens and autoantibodies in patients with systemic lupus erythematosus (SLE) and examine their associations with serological and clinical variables.
They screened human proteome arrays (>21,000 proteins) using serum from patients with SLE (n = 12) and healthy controls (n = 6) to detect IgG and IgA binding. The identified top hits were validated using ELISA in two SLE patient cohorts (cohort 1, n = 49; cohort 2, n = 46) and patients with other rheumatic diseases. Clinical associations of these autoantibodies were also examined.
The results showed top hit on the screen was Ro60, followed by 2 established SLE autoantigens and 8 new autoantigens involved in microRNA processing (Argonaute protein 1 [AGO1], AGO2, and AGO3), ribosomes (ribosomal protein lateral stalk subunit P2 and ovarian tumor deubiquitinase 5 [OTUD5]), RNA transport via the vault (major vault protein), and the immune proteasome (proteasome activator complex subunit 3). Patient serum exhibited IgG reactivity with these proteins and IgA against the AGO proteins. Based on the 95th percentile of healthy donor reactivity, 5-43% of patients had positive results for the new antigens, with OTUD5 and AGO1 having the highest positivity rates. AGO1 autoantibodies were more common in patients with oral ulcers, and IgG autoantibodies against AGO proteins were found in other rheumatic diseases.
They concluded that identifying new autoantigens in cytosolic macromolecular protein assemblies may improve understanding SLE pathogenesis and diagnosis.