Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis

Objective The study of autoantibody isotypes in autoimmune diseases is useful for identifying clinically relevant endotypes. This study was undertaken to study the prevalence and clinical significance of different isotypes and IgG subclasses of anti–peptidylarginine deiminase 4 (anti‐PAD4) autoantibodies in individuals with rheumatoid arthritis (RA). Methods In 196 RA subjects and 64 healthy controls, anti‐PAD4 antibody types were determined using enzyme‐linked immunosorbent assay. We investigated associations between anti‐PAD4 antibodies and clinical outcomes, and relevant features were confirmed in an independent RA cohort. Results Anti‐PAD4 IgG1, anti‐PAD4 IgG2, anti‐PAD4 IgG3, anti‐PAD4 IgG4, anti‐PAD4 IgA, and anti‐PAD4 IgE antibodies were more frequent in RA patients than healthy controls (P