The Importance of Non-HLA Antibodies After Heart Transplant

  • Faith Njue
  • Sharon ChihEmail author
Thoracic Transplantation (J Kobashigawa and J Patel, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Thoracic Transplantation


Purpose of Review

Antibodies to human leukocyte antigens (HLA) are associated with adverse patient and allograft outcomes after heart transplantation. Non-HLA antibodies have increasingly been recognized as important mediators of rejection, cardiac allograft vasculopathy (CAV), and allograft injury. In particular, these antibodies have been implicated in a subset of heart transplant recipients who have clinical and/or pathologic evidence of antibody-mediated rejection in the absence of detectable antibodies against HLA.

Recent Findings

Non-HLA antigens have been identified to have important roles in both the innate and adaptive immune response in transplantation. These antigens are predominantly expressed on vascular endothelium of the donor heart and include major histocompatibility class I related chain A (MICA), G protein coupled receptor angiotensin II type 1 receptor (AT1R), cytoskeletal elements such as myosin and vimentin. A growing number of studies have demonstrated antibodies to these antigens in rejection and development of CAV. At present, non-HLA antibodies are not routinely monitored post-transplant, and laboratory evaluation remains non-standardized. Further investigation is required to improve the detection of non-HLA antibodies, define pathophysiological mechanisms involved in allograft injury, and better understand their impact on clinical outcomes.


Non-HLA antibodies have been identified as important mediators of rejection, allograft dysfunction, and CAV in heart transplantation. Ongoing investigations and improving laboratory detection methods will determine their potential role in post-transplant risk stratification and management.


Non-HLA antibodies Rejection Cardiac allograft vasculopathy 



Sharon Chih is supported by a Heart and Stroke Foundation Canada Ontario Clinician Scientist Phase I award.

Compliance with Ethical Standards

Conflict of Interest

Faith Njue declares no conflict of interest.

Sharon Chih reports salary support from Heart and Stroke Foundation Canada Ontario Clinician (Scientist Phase I award), during the conduct of the study.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Heart Failure and Transplantation, Division of Cardiology, Department of MedicineUniversity of Ottawa Heart InstituteOttawaCanada

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