Elevated Serum Soluble CD137 in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis Highlights a Shared Immunoregulatory Signature

Background: Soluble CD137 (sCD137) has immunoregulatory properties and is increased in chronic inflammatory and autoimmune diseases, as well as in liver cirrhosis. Its relevance in inflammatory bowel disease (IBD) and primary sclerosing cholangitis associated with IBD (PSC-IBD) remains unclear. We measured serum sCD137 levels in IBD, PSC-IBD, PSC without IBD, and metabolic dysfunction-associated steatotic liver disease (MASLD, as a liver disease control) and assessed whether sCD137 is associated with intestinal inflammatory activity or liver disease severity. Methods: Serum sCD137 levels were measured in 77 patients with IBD, 33 with PSC-IBD, 11 with PSC without IBD, 26 with MASLD, and 78 healthy controls. In IBD, associations with serum C-reactive protein, fecal calprotectin, and symptom burden were examined. In PSC and PSC-IBD, associations with liver dysfunction and fibrosis stage, assessed by measurement of liver stiffness, were analyzed. Results: Serum sCD137 levels were higher in IBD than in controls, with similar levels in Crohn’s disease and ulcerative colitis. In IBD, sCD137 was not associated with C-reactive protein, fecal calprotectin, stool consistency, symptom extent, disease duration, or disease localization. Serum sCD137 levels were higher in PSC/PSC-IBD than in controls, patients with MASLD, and patients with isolated IBD. Patients with PSC without IBD showed similar levels to those with PSC-IBD. In PSC/PSC-IBD, serum sCD137 levels did not increase with a higher fibrosis stage. Conclusions: Serum sCD137 is a disease-associated systemic immune marker in IBD and PSC, with a stronger signal in PSC-associated disease than in isolated IBD. However, sCD137 does not reflect intestinal inflammatory activity or liver fibrosis severity in this cohort, suggesting that it captures disease-associated immune dysregulation rather than current inflammatory or fibrotic burden.