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Furthermore, rituximab significantly down\u2010regulated genes involved in immune\u2010cell recruitment, lymphoid organization alongside antigen presentation, and T cell co\u2010stimulatory pathways. In the peripheral compartment, rituximab down\u2010regulated immunoglobulins \u00a0and auto\u2010antibodies together with pro\u2010inflammatory cytokines and chemokines. Interestingly, patients classified as responders \u00a0according to\u00a0STAR displayed significantly higher baseline levels of C\u2010X\u2010C motif chemokine ligand\u201013 (CXCL13), interleukin (IL)\u201022, IL\u201017A, IL\u201017F, and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), whereas a longitudinal analysis of serum T cell\u2013related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS\u2010responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fc\u03b3\u2010receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42772-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42772","type":"journal-article","created":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T23:40:02Z","timestamp":1702251602000},"page":"763-776","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sj\u00f6gren Syndrome (CRESS) and Sj\u00f6gren Tool for Assessing 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