Mechanisms Underlying BAFF-Mediated Salivary Gland Damage in Sjögren’s Disease and Advances in Targeted Intervention

Abstract

Sjögren’s disease (SjD) is a systemic autoimmune disease characterized by lymphocytic infiltration and persistent damage to exocrine glands. Clinical symptoms vary widely among individuals, and the insidious onset of the disease makes it prone to missed or misdiagnosis. B-cell activating factor (BAFF) participates in the regulation of multiple immune signaling pathways by binding to three types of receptors: BAFF-R, TACI, and BCMA. Existing studies have confirmed that BAFF expression levels are significantly elevated in the peripheral blood and salivary gland tissues of SjD patients and are closely associated with disease activity; By activating the NF-κB, PI3K/Akt/mTOR, and JAK-STAT signaling pathways, BAFF disrupts B-cell immune tolerance, promotes the proliferation and activation of autoreactive lymphocytes, and stimulates the massive secretion of autoantibodies, thereby inducing chronic inflammation and functional damage in the glands, while simultaneously increasing the risk of secondary non-Hodgkin lymphoma in SjD patients. This article systematically reviews the naming consensus and pathological characteristics of Sjögren’s disease, elucidates the structural features of BAFF and the molecular pathways through which it mediates the pathogenesis of Sjögren’s disease, and summarizes the key role of BAFF in disease progression, thereby providing a theoretical foundation for investigating the pathogenesis of Sjögren’s disease and developing new targeted drugs.