Effect of recipient gender and donor-specific antibodies on antibody-mediated rejection after heart transplantation

Abstract

Gender‐difference regarding antibody‐mediated rejection (AMR) after heart transplantation has been described. However, no study accounted for the presence of preformed donor‐specific antibodies (pfDSA), a known risk factor of AMR, more common among women than men. In a single‐institution 6‐year cohort (2010‐2015), time to AMR was assessed, comparing men with women by survival analysis with a 1‐year death‐censored follow‐up. All AMRs were biopsy proven. Confounding variables that were accounted for included mean intensity fluorescence (MFI) of pfDSA, recipient age, HLA‐, size‐ and sex‐mismatch. 463 patients were included. Overall incidence of AMR was 10.3% at 1 year. After adjusting for confounding variables, independent risk factors of AMR were female recipient gender (adjusted hazard‐ratio [adj. HR] = 1.78 [1.06‐2.99]), P = .03) and the presence of pfDSA (adj. HR = 3.20 [1.80‐5.70], P < .001). This association remained significant when considering pfDSA by their MFI; female recipient gender had an adj. HR = 2.2 (P = .026) and MFI of pfDSA (per 1 MFI‐increase) adj. HR = 1.0002 (P < .0001). In this cohort, women were at higher risk of AMR than men and this risk increase was additive to that of pfDSA. These findings may suggest a gender‐related difference in the severity of pfDSA.

Prevalence and risk factors of having antibodies to class I and II human leukocyte antigens in older haploidentical allograft candidates

“…The association between sex and having anti-HLA antibodies has been previously reported [27][28][29][30] . Gladstone et al 30 retrospectively reviewed 957 donors to evaluate the incidence of anti-HLA antibodies and DSAs and found that the incidence of anti-HLA antibodies was higher among females than males (43.2 versus 10.8%, P < 0.0001), and DSAs were most commonly detected in female patients (30.6% versus 4.9%, P < 0.00001) among candidates for haplo-SCT.…”

“…Furthermore, Hyun et al 28 concluded that female solid organ transplantation candidates had a significantly higher PRA-positivity rate compared with that of male patients (60.3% vs 34.2%; P < 0.001). Nguyen et al 29 also found that women were at a higher risk of antibody-mediated rejection than men, and this increased risk was additive to that of preformed donor-specific antibodies after heart transplantation. Therefore, sex can be regarded as a specific risk factor for having anti-HLA antibodies and could guide their detection before SCT.…”

Quadritherapy vs standard tritherapy immunosuppressant regimen after heart transplantation: A propensity score–matched cohort analysis

“…As previously described, the presence of DSAs at the time of transplant is an independent risk factor of rejection and mortality; therefore, patients in this cohort may have been at higher risk of rejection and mortality than nonimmunized patients, which may have increase the observed treatment-effect. 11,12 This may contribute to the observed improvement in survival of patients receiving quadritherapy compared with those receiving tritherapy, as explained by the concomitant use of mTOR inhibitors with CNIs resulting in a simultaneous blockade of mTOR and calcineurin pathways with a more effective lymphocyte T inhibition than that of a single pathway. 22 Immunosuppression based on multiple pathway blockade comes in opposition to findings coming from the Tacrolimus in Combination, Tacrolimus Alone Compared (TICTAC) trial, a prospective, randomized, controlled, open-label trial comparing tacrolimus alone as maintenance immunosuppressive regimen with standard tritherapy associating MMF and tacrolimus (corticosteroids were weaned to cessation in both groups).…”

“…This work was a single‐center observational, retrospective study using a propensity score to match patients treated with quadritherapy with patients treated with tritherapy immunosuppressant regimen. Data were collected in the scope of the HEart trAnsplantation Registry of piTie‐Salpetriere University Hospital (HEARTS) registry (ClinicalTrials.gov identifier NCT03393793) 12 …”

“…Data were collected in the scope of the HEart trAnsplantation Registry of piTie-Salpetriere University Hospital (HEARTS) registry (ClinicalTrials.gov identifier NCT03393793). 12…”