Impact of Non-Human Leukocyte Antigen-Specific Antibodies in Kidney and Heart Transplantation.

Xiaohai Zhang,Nancy L Reinsmoen

doi:10.3389/fimmu.2017.00434

Abstract

The presence of donor human leukocyte antigen (HLA)-specific antibodies has been shown to be associated with graft loss and decreased patient survival, but it is not uncommon that donor-specific HLA antibodies are absent in patients with biopsy-proven antibody-mediated rejection. In this review, we focus on the latest findings on antibodies against non-HLA antigens in kidney and heart transplantation. These non-HLA antigens include myosin, vimentin, Kα1 tubulin, collagen, and angiotensin II type 1 receptor. It is suggested that the detrimental effects of HLA antibodies and non-HLA antibodies synergize together to impact graft outcome. Injury of graft by HLA antibodies can cause the exposure of neo-antigens which in turn stimulate the production of antibodies against non-HLA antigens. On the other hand, the presence of non-HLA antibodies may increase the risk for a patient to develop HLA-specific antibodies. These findings indicate it is imperative to stratify the patient’s immunologic risk by assessing both HLA and non-HLA antibodies.

Highlights

Despite the advancement of improved immunosuppression regimens and optimized patient management, antibody-mediated rejection remains a major obstacle for long-term graft survival [1]
Initial emphasis has been on the identification of human leukocyte antigen (HLA)-specific antibodies directed against the donor HLA class I and/or class II antigens
The presence of non-HLA antibodies may be tested for patients who are deemed to have a high risk of antibody-mediated rejection

Summary

INTRODUCTION

Despite the advancement of improved immunosuppression regimens and optimized patient management, antibody-mediated rejection remains a major obstacle for long-term graft survival [1]. It has been shown that 40% of patients diagnosed with biopsy-proven antibody-mediated rejection did not show donor HLA-specific antibodies in the peripheral blood [5]. These studies initiated investigation into non-HLA-specific antigens, many of which are expressed by the vascular endothelium and often revealed after stress or graft injury. Commercial reagents have become available to define antibodies to AT1R, ETAR, MICA, and endothelial cell antigens These results have been used in the clinical testing setting to investigate their impact on graft outcome. Please refer to the comprehensive review by Dr Mohanakumar in this same issue

ANTIBODIES TO MICA

ANTIBODIES TO VIMENTIN

Organ Reference Number of patients Major findings

Findings

CONCLUSION