Impact of Sex in the Efficacy of Perioperative Desensitization Procedures in Heart Transplantation: A Retrospective Cohort Study

Front Immunol. 2021 Jul 7:12:659303. doi: 10.3389/fimmu.2021.659303. eCollection 2021.

Abstract

Background: Sensitized patients, i.e. recipients with preformed donor-specific HLA antibodies (pfDSA), are at high-risk of developing antibody-mediated rejections (AMR) and dying after heart transplantation (HTx). Perioperative desensitization procedures are associated with better outcomes but can cause sensitization, which may influence their efficacy.

Methods: In sensitized patients (pfDSA>1000 mean immunofluorescence (MFI) units), we assessed the effect of perioperative desensitization by comparing treated patients to a historical control cohort. Multivariable survival analyses were performed on the time to main outcome, a composite of death and biopsy-proven AMR with 5-year follow-up.

Results: The study included 68 patients: 31 control and 37 treated patients. There was no difference in preoperative variables between the two groups, including cumulative pfDSA [4026 (1788;8725) vs 4560 (3162;13392) MFI units, p=0.28]. The cause of sensitization was pregnancy in 24/68, 35.3%, transfusion in 61/68, 89.7%, and previous HTx in 4/68, 5.9% patients. Multivariable analysis yielded significant protective association between desensitization and events (adjusted (adj.) hazard ratio (HR)=0.44 (95% confidence interval (95CI)=0.25-0.79), p=0.006) and deleterious association between cumulative pfDSA and events [per 1000-MFI increase, adj.HR=1.028 (1.002-1.053), p=0.031]. There was a sex-difference in the efficacy of desensitization: in men (n=35), the benefit was significant [unadj.HR=0.33 (95CI=0.14-0.78); p=0.01], but not in women (n=33) [unadj.HR=0.52 (0.23-1.17), p=0.11]. In terms of the number of patients treated, in men, 2.1 of patients that were treated prevented 1 event, while in women, 3.1 required treatment to prevent 1 event.

Conclusion: Perioperative desensitization was associated with fewer AMR and deaths after HTx, and efficacy was more pronounced in men than women.

Keywords: antibody mediated allograft rejection; desensitization; gender inequalities; heart transplant; sex influence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Biopsy
  • Desensitization, Immunologic* / methods
  • Female
  • Follow-Up Studies
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Rejection / therapy
  • HLA Antigens / immunology
  • Heart Transplantation* / adverse effects
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Perioperative Care* / methods
  • Pregnancy
  • Prognosis
  • Retrospective Studies
  • Sex Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • HLA Antigens
  • Immunosuppressive Agents