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  • Director of Center
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Published in Arthritis & rheumatology (Hoboken, N.J.) - 20 Jun 2022

Trutschel D, Bost P, Mariette X, Bondet V, Llibre A, Posseme C, Charbit B, Thorball CW, Jonsson R, Lessard CJ, Felten R, Ng WF, Chatenoud L, Dumortier H, Sibilia J, Fellay J, Brokstad KA, Appel S, Tarn Dr JR, Murci LQ, Mingueneau M, Meyer N, Duffy D, Schwikowski B, Gottenberg JE, ,

Link to Pubmed [PMID] – 35726083

Link to DOI – 10.1002/art.42265

Arthritis Rheumatol 2022 Jun; ():

Primary Sjögren’s syndrome (pSS) is the second most frequent systemic autoimmune disease affecting 0.1% of the general population. To characterize the molecular and clinical variability across pSS patients, we integrated transcriptomic, proteomic, cellular and genetic data with clinical phenotypes in a cohort of 351 pSS patients.Blood transcriptomes and genotypes of 351 pSS patients from a multi-center prospective clinical cohort were analyzed. Replication of the transcriptomic results was performed using 3 independent cohorts (n=462 patients). Circulating IFN-alpha (IFNɑ) and IFN-gamma (IFNγ) protein concentrations were determined using digital ELISA.Transcriptomic analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients. This finding was replicated in three independent cohorts. As gene expression analysis did not discriminate between type I and II interferons, we applied digital ELISA to demonstrate that the IFN transcriptomic signature was driven by circulating IFNɑ, and not IFNγ, protein levels. IFNɑ protein levels, detectable in 75% of patients, were significantly associated with clinical and immunological features of disease activity at enrollment, and with increased frequency of systemic complications during the 5-year follow-up. Genetic analysis revealed a significant association between IFNɑ protein levels, a MHC-II haplotype and anti-SSA antibody. Additional cellular analysis revealed that a MHC-II HLA-DQ locus acts through upregulation of HLA II molecules on conventional DCs.The present analysis identified the predominance of IFNα as driver of pSS variability and revealed an association with HLA gene polymorphisms.

https://pubmed.ncbi.nlm.nih.gov/35726083