Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation · 2026
Investigation of the Relationship Between Antibody-Mediated Rejection and Serum Interleukin 40 Levels in Heart Transplant Patients.
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Yavaşcaoğlu Üney Begüm, Ozdemir Handan, Sezgin Atila, Kavuzlu Miray, Başturk Bilkay, Verdi Hasibe
Аннотация
OBJECTIVES: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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 ).
CONCLUSIONS: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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 ).
CONCLUSIONS: 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.