Pancreatic exocrine insufficiency in patients with Sjögren's syndrome

Sjögren's Syndrome (SS) is a chronic inflammatory disorder of unknown etiology, clinically characterized by oral and ocular dryness, and histologically defined by focal lymphocytic infiltrations in lacrimal and salivary glands. The annual incidence of primary Sjögren's Syndrome (pSS) in adults ranges from 3 to 11 cases per 100,000 individuals, with a reported prevalence of 0.01%–0.72%. The disease exhibits a marked female predominance (F:M ratio = 14:1), with a mean onset age of 53.2 years. While isolated SS is classified as "primary," coexistence with another autoimmune disease defines "secondary" SS. Although primarily affecting lacrimal and salivary glands, SS may involve other exocrine glands. Given its partial exocrine function, pancreatic involvement has been documented in these patients. Exocrine Pancreatic Insufficiency (EPI) is a condition resulting from significantly reduced enzymatic activity in the gastrointestinal tract, leading to maldigestion. This deficiency may arise from decreased enzyme secretion, impaired enzyme activation, or accelerated enzyme inactivation. Although most frequently associated with advanced chronic pancreatitis, EPI has also been identified in extra-pancreatic disorders including Celiac disease, Crohn's disease, Diabetes Mellitus, and Sjögren's syndrome. Functionally and histologically, the pancreas and salivary glands share similarities; both organs produce bicarbonate-rich fluid containing digestive enzymes and other components secreted into the gastrointestinal tract. Due to structural parallels between pancreatic ductal cells and other exocrine tissues (salivary glands, bile ducts, distal renal tubules), autoantibodies against ductal cell antigens have been investigated in patients with pSS, autoimmune chronic pancreatitis, and those with both conditions. Ludwig et al. demonstrated antibodies against salivary gland ductal epithelial cells in a cohort of 12 SS patients and 31 rheumatoid arthritis (RA) patients. These antibodies were detected in 41% of SS and 33% of RA patients, with no reactivity in controls. All seropositive sera exhibited intralobular and interlobular immunofluorescence reactivity against human and monkey pancreatic ductal cells. Furthermore, these sera showed positive staining in parotid, submandibular, and lacrimal tissues from healthy controls and monkey specimens, indicating a shared antigen across examined organs. Similarly, another research group identified a monoclonal antibody targeting an antigen expressed in pancreatic ductal cells, salivary gland cells, bile ducts, and distal renal tubules in pSS patients, SS patients with chronic pancreatitis, and idiopathic chronic pancreatitis cases. This antibody was absent in chronic pancreatitis patients with other etiologies (e.g., alcohol, lithiasis). These findings support the concept of an autoantibody targeting a common ductal cell antigen, leading to the proposed terms "dry gland syndrome" or "autoimmune exocrinopathy" for seropositive patients irrespective of affected organs. Recent studies suggest that exocrine pancreatic dysfunction may occur more frequently in autoimmune diseases. However, research on the association between Sjögren's syndrome and EPI remains limited. Our study aims to contribute to early diagnosis and management strategies for SS patients, potentially improving clinical outcomes.