Strong Humoral Anti-HLA Immune Response Upon Arbitrarily Chosen Allogeneic Arterial Vessel Grafts

Abstract

Forty-three patients were grafted with forty-four fresh or cryopreserved allogeneic arterial vessels in order to treat infections of synthetic vascular implants as these often lead to sepsis, amputation and death. All the patients were HLA-typed whereas typing results of the post-mortem donors were inquired or genotyped from residuary vessels’ segments. 84% of the patients were cured from the underlying infections with a re-infection rate of only 9% attesting this therapeutic procedure a high success rate for recovering from the bacterial infections. Since the allografts were chosen without considering HLA-histocompatibility between donors and recipients 95% of the patients developed a humoral anti-HLA immune response with 89% of them giving rise to virtually definable donor-specific antibodies. Regarding the clinical outcome 16% of the patients exhibited thromboses as the most frequent complication. In addition to clinical follow up analyses of all patients, tissue excisions of 11 patients’ allografts due to various complications but not resulting from persisting infections were analyzed in order to compare these vessels’ pre-and post-transplant histological appearance. In contrast to three early excised homografts (after 14 to 45 days) all of the later on explanted vessels (after 8 to 96 months) clearly showed chronic degeneration processes induced by the alloreactive immune response. Although not leading to acute graft dysfunctions comparable to those of solid organs, arbitrarily selected vessels exhibit a high degree of alloimmunization with consequent chronic degeneration processes such as the loss of smooth muscle cells. Additionally, clear signs of fibrosis of the different arterial vessel layers lead to obliterative arteriopathy and thromboses. Thus, apparently the overall practicability of the unmatched allocation of arterial homografts is clearly limited. Further approaches of arterial vessel allo-grafting are required to investigate the hypothesis that the clinical outcome of well HLA-matched homografts may lead to a significantly decreased number of thromboses.