Donor– specific HLA-DQ antibodies may contribute to poor graft outcome after heart transplantation

Abstract

BACKGROUND: HLA-DQ donor-specific antibodies (DSA) are implicated in allograft dysfunction after renal and lung transplantation. Limited data exists on the impact of HLA-DQ antibodies on heart transplant patients. OBJECTIVE: To investigate the impact of DSA formation on allograft function and outcomes in heart transplant patients. DESIGN: Retrospective cohort study. SETTING: Collating post-transplantation patient data from computerized database in a tertiary hospital in Riyadh, Saudi Arabia from January 2006 to October 2014. PATIENTS AND METHODS: We excluded recipients with positive preoperative complement-dependent-cytotoxicity crossmatch grafts and those with preformed DSA. Anti-HLA antibodies were identified using Luminex-based assay in sera collected before transplantation with a routine endomyocardial biopsy the first year and then annually. MAIN OUTCOME MEASURES: Primary outcome measures were all-cause mortality, development of antibody mediated rejection, treated acute cellular rejection (ACR) and cardiac allograft vasculopathy (CAV). SAMPLE SIZE: 127 patients. RESULTS: DSA formation occurred in 43/127 (34%), with 33/43 (77%) targeting HLA-DQ antigens alone (n=7) or in combination with -DR, -A or B antibodies (n=26). Most (76%) were male and the mean (SD) age was 36 (14) years. Ten patients developed -A, -B or -DR antibodies without -DQ antibodies also present. Treated ACR (P=.011), reduced left ventricular ejection fraction (P<.001), CAV development (P=.003), and all-cause mortality (P=.01) were all significantly more prevalent in the DSA-positive cohort. CONCLUSION: HLA-DQ donor-specific antibodies were the most common type detected and may play a significant role in poor outcomes post-cardiac transplantation. This emphasizes the importance of HLA-DQ matching and monitoring for DSA formation in order to minimize post-transplantation immunological risk. LIMITATIONS: Retrospective design comes with inherent biases, results from single institute, with a particularly young cohort. CONFLICT OF INTEREST: None.