Background/Purpose: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by a triad of dryness, pain and fatigue in affected patients. Its diagnosis is based on a combination of clinical, histological and biological findings. Anti-Ro autoantibodies comprise reactivity against two autoantigens (Ro52 and Ro60) encoded by separate genes and found in distinct cellular compartments. When expressed in pSS, a double positivity for anti-Ro 52 and anti-Ro 60 antibodies is usually observed (2/3 of the patients), and this presentation is often associated with more systemic involvement and severe evolution, as compared to patients with a negative serology. A small proportion of patients with isolated positivity for either anti-Ro52 or anti-Ro60 antibodies are also observed, but the impact of this partial biological profile remains unclear. The aim of this study was to characterize the clinical, serological and interferon profiles of Sjögren’s patients with single anti-Ro52 or anti-Ro60 antibody positivity.

Methods:

Methods: pSS patients were recruited from the European PRECISESADS cohort (NCT02890121 and NCT02890134) and the independant Brittany DiapSS cohort (NCT03681964). Anti-Ro52 and/or anti-Ro60 antibody levels were obtained by chemiluminescence. Clinical information, disease activity, and other autoantibodies including rheumatoid factor were also collected. Type I and type II interferon signatures were generated based on previously validated scores.

Results: Anti-Ro52 and/or anti-Ro60 antibody status was obtained for 378 pSS patients. Among the latter, 254/378 (67,2%) were double positive, 80/378 (21,2%) were double negative, 21/378 (5,5%) had only anti-Ro60 antibodies and 23 (6,1%) had only anti-Ro52 antibodies. Patients with isolated anti-Ro52 antibodies had a significantly higher proportion of positive rheumatoid factor and hypergammaglobulinemia than double-negative patients (p = 0.02 and p = 0.0006, respectively), as well as a trend toward a higher inflammatory index (p = 0.08). Despite a similar trend, no significant difference was found for these parameters between isolated anti-Ro60 patients and double-negative patients. No statistical differences were found for disease activity (ESSDAI and PGA score), arthritis, sicca syndrome, glandular swelling or fatigue between the groups of single-positive patients, possibly due to the heterogeneity of patients included in terms of disease duration and drugs used. The interferon signatures according to two distinct modular scores were found to be significantly different in a graded manner with (i) the lowest interferon signature for double-negative patients, (ii) an intermediate interferon signature for patients with a single antibody positivity and (iii) a strong interferon signature for double-positive patients.

Conclusion: Taken together, these results suggest that pSS patients with single anti-Ro antibody positivity, especially anti-Ro52, adopt an intermediate phenotype between double-negative and double-positive patients, and should be considered at medium risk of disease progression.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/what-does-isolated-anti-ro52-antibody-positivity-mean-in-sjogrens-syndrome/