Abstract: Objective: The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti-Ro60/SSA antibodies, whereas the significance of anti-Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their anti-Ro52/TRIM21 antibody status.
Methods: Patients with SjD from the European PRECISESADS (n = 376) and the Brittany Diagnostic Suspicion of primitive Sjögren's Syndrome (DIApSS); (n = 146) cohorts were divided into four groups: double negative (Ro52?/Ro60?), isolated anti-Ro52/TRIM21 positive (Ro52+), isolated anti-Ro60/SSA positive (Ro60+), and double-positive (Ro52+/Ro60+) patients. Clinical information; EULAR Sjögren Syndrome Disease Activity Index, a score representing systemic activity; and biologic markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNA sequencing and type I and II interferon signatures were analyzed for PRECISESADS patients.
Results: In the DIApSS cohort, Ro52+/Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0%?11%) along with higher ?2-microglobulin (P =?0.0002), total immunoglobulin (P 0.0001), and erythrocyte sedimentation rate levels (P =?0.002) as well as rheumatoid factor (RF) positivity (66.2% vs 20.8%?25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (P =?0.046), inflammation (P =?0.005), hypergammaglobulinemia (P 0.0001), positive RF (P 0.0001), leukopenia (P =?0.004), and lymphopenia (P =?0.009) in Ro52+/Ro60+ patients. Cumulative EULAR Sjögren Syndrome Disease Activity Index results further confirmed these disparities (P =?0.002). Transcriptome analysis linked anti-Ro52/TRIM21 antibody positivity to interferon pathway activation as an underlying cause for these clinical correlations.
Conclusion: These results suggest that the combination of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies is associated with a clinical, biologic, and transcriptional profile linked to greater disease severity in SjD through the potentiation of the interferon pathway activation by anti-Ro52/TRIM21 antibodies.
Fuente: Arthritis and Rheumatology, 2024, 76(5), 751-762
Editorial: John Wiley and Sons Ltd
Año de publicación: 2024
Nº de páginas: 12
Tipo de publicación: Artículo de Revista
DOI: 10.1002/art.42789
ISSN: 2326-5205,2326-5191
Url de la publicación: https://doi.org/10.1002/art.42789