Understanding the Clinical Complexity of Sjögren’s Syndrome through High Definition Autoantibody Profiling

Authors

• A Chaturvedi
• BM Warner
• PD Burbelo

Abstract

Sjögren’s syndrome (SS) is an autoimmune disease mainly characterized by oral and ocular dryness. Some SS subjects often display a variety of extra-glandular manifestations, including hepatic, neurological, and gastrointestinal symptoms. In this study, Luciferase Immunoprecipitation Systems (LIPS), a fluid phase immunoassay, was used to analyze SS serum autoantibody responses to 12 recombinant autoantigens in a cohort of 17 healthy volunteers and 72 patients with primary SS. As expected, SS cases showed robust autoantibody responses to the three well-characterized SS autoantigens (Ro52, Ro60 and La) with an overall combined sensitivity of 67%. Additional testing revealed that certain SS patients were also seropositive for autoantibodies classically associated with other autoimmune conditions, including gastric ATPB (autoimmune gastritis), PDCE2 (primary biliary cirrhosis), RNP-A (systemic lupus erythematosus) and CENP-A (systemic sclerosis) and GAD65 (autoimmune encephalitis). The prevalence of these other autoantibodies found in SS was as follows: gastric ATPB (30.6%), PDC-E2 (15.3%), CENP-A (9.7%), GAD-65 (9.7%), RNP-A (8.3%), AQP-4 (5.6%), and interferon-alpha (2.8%). Incorporation of these additional serological targets increased the sensitivity of autoantibody testing for SS to ~80% without decreasing specificity. We are currently expanding the autoimmune screening panel to include additional autoantigen targets and are determining the clinical significance of autoantibodies to these targets in individual SS cases. The remarkable heterogeneity of autoantibodies observed in SS may represent a personalized diagnostic for SS patients and provides insight into the complex nature of this autoimmune disease.

Scientific Focus Area: Immunology

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