Comprehensive assessment of sensitizing events and anti-HLA antibody development in women awaiting kidney transplantation

Transpl Immunol. 2016 May:36:14-9. doi: 10.1016/j.trim.2016.03.002. Epub 2016 Mar 22.

Abstract

Background: Alloimmunization remains a critical factor which affects the success of kidney transplantation. Patients awaiting solid organ transplantation may develop anti-HLA antibodies after pregnancies, transfusions and previous events of transplantations.

Aim: We evaluated the effects of different sensitizing events on the anti-HLA antibody production and the potential role of patient HLA alleles in the context of antibody development in both the overall and pregnancy sensitized groups.

Material and methods: We retrospectively stratified 411 women on waiting list for kidney transplantation by route of sensitization. The presence of anti-HLA antibodies was evaluated by Solid Phase Assay and HLA typing was performed by serological and molecular methods.

Results: In our study population, 54% of women had anti-HLA antibodies. We found that the 51.6% of women with pregnancy only, 44% of women with transfusion only and 100% of women with a history of transplantation only developed anti-HLA antibodies. Pregnancy only resulted significantly associated with all anti-HLA antibody development such as anti-A, -B, -C, -DR, -DP as well as anti-DQB and -DQA antibodies. We investigated the influence of patient HLA alleles on the antibody development in the overall study population. Patients expressing HLA A*32 (p=0.024, OR=0.42), B*14 (p=0.035, OR=0.44), HLA-B*44 (p=0.026, OR=0.51) and DRB1*01 (p=0.029, OR=0.55) alleles produced anti-HLA antibodies less frequently compared to subjects with other alleles. In the pregnancy only group, B*14 (p=0.010, OR=0.12) and B*51 (p=0.005, OR=0.24) alleles were associated with a low risk of anti-HLA antibody development, while A*11 (p=0.033, OR=3.56) and DRB1*04 (p=0.022, OR=3.03) alleles seem to represent a higher risk.

Conclusions: Pregnancy still remains a strong sensitizing event in women awaiting kidney transplantation. The anti-HLA antibody development in pregnancy appears to be associated with the expression of particular HLA alleles.

Keywords: Anti-HLA antibodies; Kidney transplantation; Pregnancy; Sensitizing events; Transfusion.

MeSH terms

  • Adult
  • Alleles
  • Female
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Histocompatibility Testing / methods
  • Humans
  • Immunity, Humoral
  • Immunization
  • Immunosorbent Techniques
  • Isoantibodies / blood
  • Kidney Transplantation*
  • Middle Aged
  • Monitoring, Physiologic
  • Pathology, Molecular
  • Polymorphism, Genetic
  • Pregnancy / immunology*
  • Transplant Recipients
  • Waiting Lists

Substances

  • HLA Antigens
  • Isoantibodies