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

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.

Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study

“…Non-HLA antibodies against AT1R-Ab and ETAR-Ab were considered to be detected positive when the result was above 10 U/mL. The entire immunoassay was performed as per the manufacturer’s instructions, as previously described [ 31 ].…”

“…In addition, non-HLA antibodies are now recognized as a potential source of antibody-mediated rejection following transplantation [ 26 , 27 ]. The intricate role of non-HLA antibodies in allograft rejection and vasculopathy has been described in our earlier studies [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The epitopes that lead to the production of these antibodies typically result from tissue disruption, specifically of the endothelium, secondary to prior inflammation and injury [ 29 , 34 ].…”

Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

“…Most hand transplant recipients rarely experience ABMR; however, a few reports have emerged attributing vascular rejection to the presence of anti-AT 1 R and other non-HLA antibodies (47,48,69). Banasik et al investigated the presence of non-HLA antibodies in the post-transplant serum samples of five hand transplant patients (47).…”

“…Very recently, Sikorska et al investigated the role of non-HLA antibodies in hand transplant rejection (48). The post-transplant serum samples from six hand transplant recipients were assayed for antibodies against AT 1 R, ETAR, protease-activated receptor 1 (PAR-1), and vascular endothelial growth factor A (VECGF-A) using commercial ELISAs.…”

Chronic Active T-Cell Mediated Kidney Rejection as a Clinically Significant Type of Allograft Loss?

“…Moreover, recent studies compelling clinical and experimental findings suggest that non-HLA antibodies directed against autoantigens may contribute to both acute and chronic ABMR [ 35 ]. Moreover, the presence of non-HLA antibodies does not only refer to kidney graft loss but has also been found in other transplant rejection types such as hand allografts rejection [ 36 ]. T cells play a very important role in the formation of non-HLA antibodies.…”