Significance of Anti-HLA Antibodies on Adult and Pediatric Heart Allograft Outcomes

Abstract

As methods for human leukocyte antigens (HLA) antibody detection have evolved and newer solid phase assays are much more sensitive, the last 15 years has seen a renewed focus on the importance of HLA antibodies in solid organ transplant rejection. However, there is still much controversy regarding the clinical significance of antibody level as depicted by the mean fluorescence intensity of a patient’s neat serum. Emerging techniques, including those that identify antibody level and function, show promise for the detection of individuals at risk of allograft rejection, determination of the effectiveness of desensitization prior to transplant, and for monitoring treatment of rejection. Here, we review current publications regarding the relevance of donor-specific HLA antibodies (DSA) in adult and pediatric heart transplantation (HT) with graft survival, development of antibody-mediated rejection and cardiac allograft vasculopathy (CAV). The negative impact of DSA on patient and allograft survival is evident in adult and pediatric HT recipients. Many questions remain regarding the most appropriate frequency of assessment of pre- and posttransplant DSA as well as the phenotype of DSA memory vs. true de novo antibody using large multicenter adult and pediatric cohorts and state-of-the-art methodologies for DSA detection and characterization.

Antibody Based Therapy in Coronary Artery Disease and Heart Failure

“…All are thought to be either antibody dependent or at least involve antibody mediated responses. 21 Hyperacute rejection is stimulated by preexisting antibodies to the donor heart (donor specific antibodies (DSA)) in the recipient and is a powerful and rapid response occurring via activation of the complement system. The risk of this can be lowered to some extent by avoiding transplantation of donor tissues into a patient who is already sensitised to the donor.…”

“…concentric arterial narrowing. 21 First-line treatments include anti-inflammatories such as methylprednisolone, removal of immunogenic antibodies by plasmapheresis and intravenous immunoglobulin transfusion for desensitisation with or without anti-thymocyte globulin to reduce T lymphocyte levels. Anti-lymphocyte antibodies to the cell surface marker CD52 to deplete B and T cell levels can also be used.…”

“…Antibody-mediated cardiac rejection is the most common cause of death within the first 5 years after transplant. 21 In the case of MI, survivors are at high risk for death, or recurrent MI and other cardiovascular events. 25,26 Although, patient outcome is improving, there is considerable burden on healthcare systems and incidence is increasing in an aging and obese population.…”

“…22 mAbs are suggested as a treatment to suppress formation of de novo donor-specific antibodies following transplantation and for general immunosuppression. 21,22 Rituximab, a B cell suppression agent currently approved for cancer and arthritis has been suggested for this use though has not been trialled in this context, and it should be noted it is not recommended for patients with arrhythmia. [21][22][23] As mentioned above in the context of atherosclerosis, the IL-1β neutralising mAb canakinumab is also being trialled in heart failure patients secondary to MI.…”

“…21,22 Rituximab, a B cell suppression agent currently approved for cancer and arthritis has been suggested for this use though has not been trialled in this context, and it should be noted it is not recommended for patients with arrhythmia. [21][22][23] As mentioned above in the context of atherosclerosis, the IL-1β neutralising mAb canakinumab is also being trialled in heart failure patients secondary to MI. 16 The main study, CAN-TOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) is designed to assess whether recurrent cardiovascular events can be reduced in high risk patients, defined as those with persistent high sensitivity CRP elevation.…”