Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation.

Dorota Sikorska,Mirosław Banasik,Jerzy Jabłecki,Kai Schulze-Forster,Rafał Rutkowski,Włodzimierz Samborski,Andrzej Oko,Katarzyna Korybalska,Przemysław Daroszewski,Rusan Catar,Harald Heidecke,Dorota Kamińska,Mariusz Kusztal,Joanna Łuczak

doi:10.3390/jcm11030833

Abstract

The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

Highlights

The results in vascularized composite allotransplantation (VCA) are promising but acute rejection rates are higher than in solid organs recipients, making it a clinically significant problem in VCA [1,2]
The pathologic changes somewhat differ according to the organ considered, a frequent feature of chronic rejection is injury of blood vessels, which may lead to graft vasculopathy
In the previous article we described the presence of non-human leukocyte antigen (HLA) antibodies in combination with the occurrence of multiple rejection episodes found in one patient after bilateral hand transplantation [22]

Summary

Introduction

The results in vascularized composite allotransplantation (VCA) are promising but acute rejection rates are higher than in solid organs recipients, making it a clinically significant problem in VCA [1,2]. Chronic rejection, including vasculopathy, were reported in more long-term VCA [4,5], chronic changes such as dermal capillary thromboses with C4d deposits in cutaneous capillaries have been seen [6] It seems that in VCA, both acute and chronic rejection is a clinically significant problem and the development of graft vasculopathy may play a role in the long-term deterioration of hand allografts [7,8]. The pathologic changes somewhat differ according to the organ considered, a frequent feature of chronic rejection is injury of blood vessels, which may lead to graft vasculopathy This vasculopathy is thought to be caused by low-grade inflammation-induced endothelial damage and chronic remodeling of smooth muscle cells in an attempt to heal this damage. These vasculopathy patterns seem to reflect the microangiopathy observed in patients with active systemic sclerosis [9]

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