Pathogenesis of renal involvement in primary Sjögren’s disease: convergence of multifactorial mechanisms on immune dysregulation

Primary Sjögren's disease (pSjD) is a chronic systemic autoimmune disease in which immune-mediated pathology is not confined to exocrine glands but also affects multiple organ systems. Renal involvement constitutes a clinically meaningful manifestation of pSjD and may exert a considerable impact on disease progression, prognosis, and treatment selection. However, the pathogenic basis of renal injury in pSjD is still incompletely understood, and existing therapeutic approaches remain largely empirical. Available studies suggest that renal involvement in pSjD arises from the interaction of multiple determinants, including inherited susceptibility, environmental factors, and endocrine dysregulation. At the core of these pathogenic mechanisms lies persistent activation of the type I interferon (IFN-I) system and immune dysregulation driven by excessive responses of T and B lymphocytes. Such immune abnormalities favor sustained autoantibody production and ectopic germinal center (EGC) formation, thereby amplifying autoimmune inflammation and promoting renal structural and functional injury. Here, this review integrates relevant literature to examine the multifactorial pathogenic mechanisms described above and to systematically elucidate how these mechanisms drive autoimmune responses through diverse immune cell populations. In addition, the potential application prospects of relevant novel targeted therapeutic strategies in pSjD-related renal damage are discussed.