Soluble CD137 in health and disease: A systematic review and meta-analysis.

e14528 Background: Soluble CD137 (sCD137), produced by regulatory T cells, plays a critical role in immune response regulation. Its measured presence in serum highlights sCD137 as a potential biomarker for diagnosis and treatment monitoring across several conditions, including autoimmunity, cancer, and infectious diseases. However, inconsistent findings across studies call for a systematic review to clarify its clinical value. Methods: Following PRISMA guidelines, a comprehensive search across medical databases identified studies on sCD137 in healthy and diseased patients. Two researchers independently screened, extracted data, and assessed study quality. We conducted a random-effects meta-analysis to estimate the pooled standardized mean difference (SMD) between patient groups and healthy controls, as well as the change in sCD137 levels pre- and post-treatment. Meta-regression analysis was conducted to study the effect of age, geographical location, study design, and measurement technique on sCD137 levels. Results: A total of 47 articles and 4854 individuals were included in the analysis, encompassing a diverse range of study designs, diseases, and treatments. We found diseased patients exhibited higher levels of sCD137 than healthy controls (SMD: 1.08, 95% CI, 0.71 to 1.44). More specifically, elevations in sCD137 was more prominent in patients with infectious conditions (SMD: 1.78, 95% CI, 0.08 to 3.47) and gastrointestinal and genitourinary syndromes (SMD: 1.30, 95% CI, 0.12 to 2.48), while cancer (SMD: 0.79, 95% CI, 0.23 to 1.34) and autoimmune diseases (SMD: 0.73, 95% CI, 0.03 to 1.43) had lower magnitude elevations. Pre- and post-treatment analysis demonstrated that therapy reduced the levels of sCD137 in autoimmunity (SMD: -0.73, 95% CI, -1.24 to -0.23), whereas cancer therapies had the opposite effect (SMD: 1.14, 95% CI, 0.60 to 1.67). Age, geographical location, epidemiological design, or sCD137 measurement technique did not influence pooled estimations. Conclusions: Soluble CD137 emerges as a reliable biomarker for differentiating healthy individuals from diseased patients. In patients with cancer or autoimmune disease, longitudinal changes in sCD137 offer a valuable approach for tracking treatment responses. Given that sCD137 release reflects internal immunoregulatory pressures, disease and therapeutic contexts must be considered when making clinical interpretations.