Sjögren Disease-B Cells at the Brink: From Autoimmunity to Lymphomagenesis and the Rise of Novel B Cell-Targeted Therapies.

Abstract

Sjögren disease (SjD) is a common systemic autoimmune disorder characterized by inflammation of the exocrine glands, resulting in dryness. Patients frequently exhibit extraglandular manifestations affecting various organ systems. To date, there are no FDA-approved disease-modifying therapies for SjD. In this review, we explore the expanding field of SjD endotyping as a tool to enhance patient stratification, prognostication, and clinical decision-making. SjD endotypes driven by heightened B cell activity are linked to increased lymphoma risk. B cells play a central role in SjD pathogenesis by producing autoantibodies, presenting antigens, and releasing pro-inflammatory cytokines. These functions contribute not only to autoimmunity but also to lymphomatous transformation. We illustrate these concepts through the case of a patient with SjD who developed parotid MALT lymphoma after years of recurrent glandular swelling-highlighting a common yet challenging scenario for practicing rheumatologists. Using this case as a framework, we examine the pathobiology of B cells in SjD that drive autoreactivity and lymphomagenesis. Finally, we review emerging B cell-targeted therapies that reflect a broader shift in the SjD treatment landscape from symptomatic management to targeted therapies grounded in disease immunopathology.