Sex differences in preformed panel‐reactive antibody levels and outcomes in patients undergoing heart transplantation

Abstract

Antibody-mediated immune processes play a key role in outcomes after heart transplantation. Panel-reactive antibodies (PRA) are circulating anti-human leukocyte antigen (HLA) antibodies directed against the donor major histocompatibility complex class I and II antigens that are expressed on allograft endothelial cells. 1,2 PRA levels of ≥10% indicate allosensitization, 3 a relevant risk factor for adverse outcomes. To date, only a small fraction of heart transplant recipients has relevant values of preformed antibodies. 4 However, allosensitization is an emerging problem due to the increasing use of ventricular assist devices (VAD) that induce PRA formation. 5,6 Besides VAD therapy, previous pregnancies, 6,7 blood product transfusions, 2,8 or prior heart transplantation cause allosensitization. Abstract Background: Sex differences in panel-reactive antibody (PRA) levels in heart transplant recipients and their association with transplant-related outcomes are mostly unknown. Methods: In 20 181 (24.7% women) first-time heart transplant recipients included from July 2004 to March 2015 in the prospective Organ Procurement and Transplantation Network (OPTN), we studied sex differences in most recent (mr) and peak (p)PRA and outcomes (graft failure, rejection, cardiac allograft vasculopathy [CAV], retransplantation, and mortality). Median follow-up (all-cause mortality) was 6 years. Analyses are based on OPTN data (March 6, 2017).Results: MrPRA levels were associated with all-cause mortality (hazard ratio, 95% confidence interval: class I 1.03, 1.01-1.04, P < 0.001) and acute rejection (class II 1.08, 1.03-1.14, P = 0.0044). PPRA levels were associated with all-cause mortality (class I 1.02, 1.00-1.04, P = 0.015) and CAV (class II 1.03, 1.01-1.06, P = 0.020). Sex interactions were seen for the association of pPRA and graft failure with a higher risk in women, and for pPRA and CAV with a higher risk in men.Conclusions: PRA were associated with different transplant-related outcomes in both sexes. However, women with elevated pPRA were shown to be at higher risk for graft failure, whereas higher levels of pPRA were more hazardous for men in developing CAV. K E Y W O R D Sheart transplantation, outcomes, panel-reactive antibodies, sex differences

Arteriovenous Fistula Nonmaturation: What’s the Immune System Got to Do with It?

“…Higher PRA levels have been reported in Black compared with White populations, but sex imbalances between Black and White study participants may contribute to this perceived racial disparity (28,29). Elevated PRA are also associated with increased cardiovascular mortality in patients with ESKD (30). For example, a recent study observed that higher PRA was an independent predictor of cardiovascular and all-cause mortality among over 160,000 patients waitlisted for a kidney transplant (21).…”