Beyond Titer: Expanding the Scope of Clinical Autoantibody Testing

Autoantibodies that bind self-antigens are a hallmark of autoimmune diseases, but can also be present in healthy individuals. Clinical assays that detect and titer antigen-specific autoantibodies are an important component of the diagnosis and monitoring of autoimmune diseases. Autoantibodies may contribute to disease pathogenesis via effector functions that are dictated by both the antigen-binding site and constant domain.In this review, we discuss features of antibodies, in addition to antigen-binding specificity, which determine effector function. These features include class, subclass, allotype, and glycosylation. We discuss emerging data indicating that analysis of these antibody features may be informative for diagnosis and monitoring of autoimmune diseases. We also consider methodologies to interrogate these features and consider how they could be implemented in the clinical laboratory.Future autoantibody assays may incorporate assessment of additional antibody features that contribute to autoimmune disease pathogenesis and provide added clinical value.