Anti-HLA-A, -B, -DR, -DQB1 and -DQA1 antibodies reactive epitope determination with HLAMatchmaker in multipare awaiting list for heart transplant

Hum Immunol. 2013 Aug;74(8):937-41. doi: 10.1016/j.humimm.2013.04.033. Epub 2013 Apr 27.

Abstract

Human leukocyte antigen (HLA) antibodies represent a significant risk factor for transplant failure. It is very important to characterize anti-HLA antibodies as epitopes rather than antigens so that this knowledge can be applied clinically. The aim of the study was to investigate the extra reactivity patterns in sensitized multipare. Here, we have used the HLAMatchmaker program, a theoretical algorithm, to explain these unexpected antibody reactivity patterns in multipare awaiting for heart transplant. The patient was sensitized during pregnancy by alleles HLA-A(*)24:02, HLA-DRB1(*)07:01, HLA-DRB4(*)01:01, DQB1(*)02:02 and DQA1(*)02:01 mismatches with development of respective antibodies. However, the patient' sera were shown an unexpected reactivity not directed toward HLA mismatches of daughters: A(∗)23:01, A(*)24:03 and B(*)15:12 for class I and DRB4(*)01:03, DRB1(*)09:02, DRB1(*)09:01, DQB1(*)03:01, DQB1(*)03:03, DQB1(*)03:02, DQB1(*)04:02, DQB1(*)04:01 and DQB1(*)02:01 for class II. By HLAMatchmaker analysis we found that these antibodies reacted with eplet shared by antigens in single allele Luminex panels. These eplets were: 62EE, 66GKH, 70KAH, 71HS, 127K, 113YH, 144KR, 150AAH, 151AHV, 163TG and 167DG for class I and 4Q, 74RRAE, 71RRA, 98KN, 120N, and 135G, 25FT, 34HE, 41ER, 47EK2, 48LF for class II. Thus, HLAMatchmaker software together with to solid phase techniques could open new horizons for a more precise characterization of the HLA-antibodies.

Keywords: CDC; CDR; ELISA; HLA; MFI; PCR-SSP; PRA; SA; complement-dependent cytotoxicity crossmatch; complementary determining region; enzyme-linked immunosorbent assay; human leukocyte antigen; mean fluorescence intensity units; panel reactive antibody; polymerase chain reaction-sequence-specific primer; single antigens.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alleles
  • Antibodies / immunology*
  • Antibody Specificity / genetics
  • Antibody Specificity / immunology
  • Epitopes / immunology*
  • Female
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Heart Transplantation*
  • Histocompatibility / genetics
  • Histocompatibility / immunology
  • Histocompatibility Testing*
  • Humans
  • Middle Aged

Substances

  • Antibodies
  • Epitopes
  • HLA Antigens