OR39: UTILITY OF ASSESSING THE C1Q BINDING ABILITY OF HLA ANTIBODIES IN MAXIMIZING DONOR POOLS AND PREDICTING RISK OF TRANSPLANT-RELATED MORBIDITY IN HEART TRANSPLANT

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Pre-transplant (txp) sensitization in patients awaiting heart transplants put them at an increased risk post-txp of mortality, rejection, and chronic allograft vasculopathy and also reduces the pool of available donors. Many of the deleterious effects of the HLA antibodies (abs) are associated with their ability to activate the complement cascade. Recent reports have highlighted the correlation between C1q-binding donor-specific HLA abs (DSA) and the increased incidence of antibody-mediated rejection (AMR) and graft loss. It has been suggested that pre-txp identification of DSA that bind C1q will allow for better prediction of the suitability of a potential donor. We present a case report of a broadly sensitized heart txp patient (cPRA = 88%; MFI cutoff = 3,000). Based on the patient’s critical condition and to maximize opportunities for receiving suitable donor offer, MFI levels for unacceptable antigens were raised to 6,000 and a prospective flow cytometric crossmatch requirement was instituted. A low positive T- and B-cell crossmatch was observed with all sera specimen tested and was likely due to the presence of DSA against B49 and B57 (MFI = 4,000–5,000). Patient underwent intraoperative IVIG/plasmapheresis and the txp surgery proceeded without incident. Three weeks post-txp patient developed biopsy proven (strongly and diffusely C4d+) AMR without any concomitant increase in the titers of the DSA. Retrospective study was initiated to compare of the ability of the detected, pre-txp and post-txp HLA abs to bind C1q using single-HLA-antigen-coated beads. Results indicated that HLA abs observed in the pre-txp specimen did not bind C1q, even in the presence of AHG. Significantly and in sharp contrast, isotype switching was evident in the post-txp specimen. Several HLA abs including the DSA (B49) displayed an increased ability to bind C1q. This study highlights 2 important facets of assessing the relevance of identifying the complement-activating ability of HLA abs. Firstly, it suggests that evaluating the presence/absence of C1q binding HLA abs may provide important information to analyze the suitability of a potential donor. Secondly and in contrast, it suggests that evaluating pre-transplant isotype of potential DSA are of limited efficacy in predicting the AMR-free duration post-txp.