AUTHOR=Casadó-Llombart Sergi , Gheitasi Hoda , Ariño Silvia , Consuegra-Fernández Marta , Armiger-Borràs Noelia , Kostov Belchin , Ramos-Casals Manuel , Brito-Zerón Pilar , Lozano Francisco 

TITLE=Gene Variation at Immunomodulatory and Cell Adhesion Molecules Loci Impacts Primary Sjögren's Syndrome

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.822290

DOI=10.3389/fmed.2022.822290

ISSN=2296-858X

ABSTRACT=<p>Primary Sjögren's syndrome (pSS) is an autoimmune disease triggered by a combination of environmental and host genetic factors, which results in the focal lymphocytic infiltration of exocrine glands causing eye and mouth dryness. Glandular infiltrates include T and B cell subsets positive for CD5 and/or CD6, two surface scavenger receptors involved in the fine-tuning of intracellular signals mediated by the antigen-specific receptor complex of T (TCR) and B (BCR) cells. Moreover, the epithelial cells of inflamed glands overexpress CD166/ALCAM, a CD6 ligand involved in homo and heterotypic cell adhesion interactions. All this, together with the reported association of functionally relevant single nucleotide polymorphisms (SNPs) of <italic>CD5, CD6</italic>, and <italic>CD166/ALCAM</italic> with the risk or prognosis of some immune-mediated inflammatory disorders, led us to investigate similar associations in a local cohort of patients with pSS. The logistic regression analyses of individual SNPs showed the association of <italic>CD5</italic> rs2241002<sup>T</sup> with anti-Ro/La positivity, <italic>CD6</italic> rs17824933<sup>C</sup> with neutropenia, and <italic>CD6</italic> rs11230563<sup>T</sup> with increased leukopenia and neutropenia but decreased peripheral nervous system EULAR Sjögren's syndrome disease activity index (ESSDAI). Further analyses showed the association of haplotypes from <italic>CD5</italic> (rs2241002<sup>T</sup>-rs2229177<sup>C</sup>) with anemia and thrombocytopenia, <italic>CD6</italic> (rs17824933<sup>G</sup>-rs11230563<sup>C</sup>-rs12360861<sup>G</sup>) with cutaneous ESSDAI, and <italic>CD166/ALCAM</italic> (rs6437585<sup>C</sup>-rs579565<sup>A</sup>-rs1044243<sup>C</sup> and rs6437585<sup>C</sup>-rs579565<sup>G</sup>-rs1044243<sup>T</sup>) with disease susceptibility and several analytical parameters (anti-nuclear antibodies, neurological ESSDAI, and hematologic cytopenias). These results support the relevance of gene variation at loci coding for cell surface receptors involved in the modulation of T and B lymphocyte activation (<italic>CD5, CD6</italic>) and epithelial-immune cell adhesion (<italic>CD166/ALCAM</italic>) in modulating the clinical and analytical outcomes in patients with pSS.</p>