Cardiac Non-Human Leukocyte Antigen Identification: Techniques and Troubles

Abstract

Historically efforts have focused on the human leukocyte antigen (HLA) as the major cause for acute and chronic rejection following cardiac transplantation. However, rising evidence indicates that non-HLA antibodies can be both primary initiators and modifiers of antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV). The purpose of this review is to assess currently available technologies for non-HLA identification and leveraging such responses toward antibody quantification. Several techniques have been used to identify antigenic determinants of recipient graft-specific non-HLA humoral immune responses, but each comes with its own set of benefits and caveats. Improving our ability to detect non-HLA humoral immune response will aid in our understanding of the underlying antigenic determinants of AMR and CAV, as well as improve patient outcomes.

Small Diameter Xenogeneic Extracellular Matrix Scaffolds for Vascular Applications

“…92,96,97 This topic is reviewed in detail elsewhere. 98 Regardless of the type of antibody response, failure to eliminate antigens results in increased risk of scaffold immune destruction. Antibodies bind to remnant antigens in xenogeneic scaffolds, initiating recruitment of both adaptive and innate immune cells.…”

“…Existence of noncellular antigens and demonstration of persistence of cellular antigens in apparent acellular scaffolds have brought into question the applicability of decellularization as the primary outcome measure in ECM scaffold production. 98,185 Indeed, this concern has led to an increasing emphasis on assessment of both known (e.g., a-gal, MHC I) and unknown (e.g., total minor histocompatibility antigens) content of acellular ECM scaffolds. 91,116,[186][187][188] Decellularization processes employ an array of mechanisms, including mechanical, osmotic, chemical, and/or enzymatic agents, which can be enhanced and/or combined to achieve better decellularization results.…”

Shotgun Immunoproteomics for Identification of Nonhuman Leukocyte Antigens Associated With Cellular Dysfunction in Heart Transplant Rejection

“…15 Previous research into cardiac non-HLA has used suboptimal methods for antigen identification, generally using endpoint studies focused on a single antigen. 23,24 Considering the time-sensitive nature of acute rejection and the need to differentiate primary initiators of rejection versus secondary bystanders, longitudinal time-course studies are essential. The current study uses a novel affinity chromatography immunoproteomic approach to determine longitudinal response toward multiple non-HLA targets, thereby overcoming the limitations of previous studies.…”

Management of heart transplant recipients with hemodynamically significant clinical rejection in the presence of antibodies against angiotensin II type 1 receptor: A retrospective study

“…Antibodies against the human leukocyte antigens (HLA) are known to play a dominant role in decreased graft survival [2] and treatments prior to and after transplantation are used for patients who present with HLA antibodies directed against donor antigens (HLA-DSA) [3]. Many centers also report testing for presence of antibodies other than HLA (non-HLA antibodies) when allograft dysfunction occurs in the absence of detectable HLA-DSA [4,5]; these include antibodies directed against the MHC class I polypeptiderelated sequence A [6], endothelin A receptor [7], vimentin and myosin [8]. However, appropriate treatment approaches or outcomes posttreatment in the presence of non-HLA antibodies are not sufficiently described in the literature [3].…”