Investigation of the Relationship Between Antibody-Mediated Rejection and Serum Interleukin 40 Levels in Heart Transplant Patients

Heart transplant remains the definitive treatment for end -stage heart failure; however, long -term graft survival is often compromised by immune -mediated injury. Antibody -mediated rejection is primarily driven by donor -specific antibodies synthesized by Blymphocytes. Interleukin 40 has been associated with B -cell -mediated autoimmune pathologies, suggesting a role in donor -specific antibody development and posttransplant outcomes. We evaluated interleukin 40 levels, B -cell phenotypic changes, and rejection in heart transplant recipients.

In this clinical cohort analysis with ex vivo cell culture, we quantified serum interleukin 40 levels (enzyme -linked immunosorbent assay ) in control and recipient groups (nonrejection, active rejection {pretreatment }, and postdesensitization ). Ex vivo assays involved incubating donor lymphocytes with autologous serum or serum positive for donor-specific antibodies, followed by culture supernatant assays. We analyzed B -cell markers (CD19, CD20, CD21, CD45, HLA DR ) by flow cytometry at baseline, 6 hours, and 24 hours across serial dilutions of donor-specific antibodies.

Serum interleukin 40 levels were significantly lower in stable recipients versus control and rejection patients (P < .001 ). Among rejection patients, interleukin 40 levels increased significantly posttreatment (P = .039 ). Ex vivo exposure to serum positive for donor -specific antibodies downregulated B -cell markers, particularly CD21, consistent with a transition toward a memory B -cell phenotype. Although HLA DR expression remained stable in control and autologous serum cultures, expression significantly decreased in the presence of donor -specific antibodies at 6 and 24 hours (ie, donor -specific antibodies induced significant B -cell phenotypic alterations ).

Interleukin 40 appears closely linked to B -cell dynamics and antibody -mediated rejection pathophysiology in heart transplant. Suppressed interleukin 40 levels observed in stable recipients contrasted with posttreatment elevations in rejection patients, highlighting interleukin 40 as a potential biomarker for monitoring desensitization efficacy and graft immune status. Further multicenter prospective studies are warranted to evaluate interleukin 40 kinetics alongside established biomarkers for clinical utility in posttransplant surveillance.