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.

Immunosuppressive protocols with tacrolimus after cryopreserved aortal allotransplantation in rats

“…Despite of it, is the use of immunosuppression in patients after clinical arterial allograft implantation not generally accepted by vascular surgeons [ 1 ]. This is probably caused by no acceptance of the antigenicity of arterial allografts by vascular surgeons [ 9 ] and/or a reluctance to use immunosuppressive treatment in patients with ongoing infection [ 31 ]. However, if the immunosuppressive therapy after clinical arterial transplantation is used, the drug most commonly used is cyclosporine A [ 32 ].…”

“…In the recently published work of Konrad H. et al was clearly demonstrated that cryopreserved arterial allografts used in clinical practice are highly immunogenic in terms of an HLA-directed immune response. This allogeneic immune response does not lead to an acute graft loss but to a chronic vascular degeneration process with clinically apparent thromboses with subsequent medical interventions up to amputations [ 9 ]. The low dose immunosuppression with sirolimus (mammalian target of rapamycine inhibitor) did not show any affective influence on antibody-mediated rejection of these cryopreserved arterial allografts.…”

“…After transplantation of cold-stored and cryopreserved arteries we can observe immune reaction similar to the rejection process in solid organ transplantation [ 8 , 9 ]. In patients after transplantation of arterial allografts with no immunosuppression we can find a higher incidence of graft related complication as graft ruptures, graft aneurysm formation or thrombosis [ 2 ].…”

“…Even though immunosuppression can improve results after allograft transplantation this therapy is not generally accepted. This is probably caused by wariness to decrease immune reaction in patients with florid infection [ 9 , 13 ].…”

Influence of the new standardized clinical cryopreservation/slow thawing protocol on immunogenicity of arterial allografts in rats

“…The experimental and clinical studies revealed strong antigenicity of both cold-stored and cryopreserved allografts, respectively [10,11]. This immunogenicity is responsible for late graft-related complication presented as graft dilatation, rupture or thrombosis [12].…”