Immune Profiling of Decellularized Homograft Degeneration: Insights from Plasma and Tissue Cytokine Analysis

All articles of this category (opens in new window) Background: Decellularized homograft valves (DHVs) combine durability, regenerative capacity, and growth potential without anticoagulation, representing an attractive alternative to mechanical or biological prostheses, especially in young patients. Despite encouraging outcomes, some patients develop acute or chronic degeneration requiring reoperation, suggesting an immunological rejection of the implanted valves despite donor cell removal. Methods: We prospectively studied 21 patients undergoing DHV implantation. Serial blood samples were obtained preoperatively (D0) and on postoperative days 1, 7, and 30 for multiplex analysis of 56 cytokines and proteins. In addition, six degenerated DH vs. (four aortic, two pulmonary) explanted at reoperation were analyzed for tissue cytokine analysis. Correlation matrices and hierarchical clustering were applied to identify co-secretion patterns. Results: Patients with degenerated DH vs. exhibited significantly elevated plasma levels of endothelial receptors (LEPR, LDLR, IGF1R, ADAM15) and macrophage-related proteins (sCD163, PLA2G7, CHGA). These markers formed distinct clusters partially overlapping with native aortic valve stenosis. In contrast, adaptive immune cytokines (IL-1β, IL-2, IL-4, IL-7, IL-10, IL-13, IL-17, IFN-γ) were consistently low in both plasma and tissue, showing no evidence of T- or B-cell activation. Serial postoperative measurements revealed transient inflammatory peaks (sIL-2Rα, sTNFRI/II, IL-6, IL-1RA, IL-8) on day 1, declining by day 30, consistent with cardiopulmonary bypass-related inflammation. Longitudinal clustering demonstrated dynamic reorganization, incorporating proteins linked to angiogenesis and extracellular matrix remodeling (sVEGFR2, sVEGFR3, SYND4, IL-9) by day 30. Tissue analysis confirmed elevated levels of HSP60, LDLR, sCD163, ADAM15, PLA2G7, and PTGDS in both plasma and explanted valves. Comparable cytokine levels were observed in leaflets, homograft wall, and even adjacent native pulmonary artery tissue, suggesting extension of immune system activation beyond the graft itself. No differences in cytokine dynamics were observed between aortic vs. pulmonary homografts or between primary vs. repeat implantations. Conclusion: End-stage DHV degeneration is characterized by specific endothelial and macrophage-related protein clusters, while adaptive immune activation is absent. Elevated markers were consistently detected in both plasma and degenerated tissue, with similar profiles across leaflets, homograft wall, and adjacent native vessel. These findings provide new mechanistic insights into the pathogenesis of decellularized homograft degeneration. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany