Cytokine Profile in Patients with Chronic Granulomatous Disease (CGD)

Introduction CGD is an inborn error of immunity that results in severe, recurrent bacterial and fungal infections, immune dysregulation, and chronic inflammation. Profiling the cytokine signature in CGD patients may inform allogeneic hematopoietic stem cell transplantation (allo-HSCT) or experimental gene therapy strategies. Methods A single blood draw was obtained in an observational clinical trial (NCT06605378) of patients in the United States and the United Kingdom confirmed to have CGD but had not previously undergone allo-HSCT or gene therapy. Serum cytokine levels were measured by Meso Scale Discovery (MSD) multiplex cytokine assay and enzyme-linked immunosorbent assay (ELISA) as a surrogate marker for cellular cytokine signatures. Results As of October 2025, 36 participants (median age 26, range 1–54 years; 33% under 18 years of age; 83% male, 11% Hispanic or Latino, 8% Asian, and 6% Black) with CGD (75% with mutations in CYBB) had cytokine results for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, and CXCL9. In adults (≥18 years of age), there were higher levels of CXCL9 (1.7-fold), IFN-γ (5.4-fold), IL-6 (4.8-fold), and IL-8 (1.1-fold) compared to pediatric participants (<18 years of age). In participants with mutations in CYBB, there were higher levels of CXCL9 (1.1-fold), IFN-γ (3.6-fold), and IL-6 (3.9-fold) with lower levels of IL-8 (0.6-fold) compared to those with mutations in other genes. Other cytokines did not appear different between groups. The impact of clinical status, including active infections or inflammatory complications, is still being analyzed. Small numbers prevented formal comparisons. Conclusion Cytokine profiles in CGD patients appear to vary with age and genotype. Further research is needed to compare these profiles with healthy controls and to elucidate the impact of these profiles on allo-HSCT or gene therapy outcomes. Understanding these differences may lead to more tailored therapeutic approaches for CGD patients.