Helper and cytotoxic T cell precursor frequencies are not predictive for development of acute graft-versus-host disease after partially T cell-depleted HLA-identical sibling BMT

Bone Marrow Transplant. 1998 Dec;22(11):1049-55. doi: 10.1038/sj.bmt.1701489.

Abstract

Despite the use of partially T cell-depleted grafts, 20% of the recipients of an HLA-identical sibling marrow graft develop aGVHD > or = II. This indicates that the current method for selecting a sibling donor, ie serological typing for HLA-A, B and DR, and a mixed lymphocyte culture (MLC) or molecular typing for HLA-DRB/DQB, is not predictive for aGVHD. In order to optimise our selection procedure, we retrospectively analysed patients who developed aGVHD > or = II by means of sequencing based typing for HLA-DPB and frequency analysis of alloreactive helper and cytotoxic T lymphocyte precursors (HTLp-f and CTLp-f). Patients who did not develop aGVHD or developed aGVHD grade I served as controls. Retrospective typing for HLA-DPB revealed only a single disparity in the group with aGVHD > or = II, indicating that mismatches for antigens other than HLA are the major cause of aGVHD in these patients. Furthermore, in our patient group, neither HTLp-f nor CTLp-f were predictive for development of aGVHD indicating that these assays in their current set-up are insufficiently sensitive to predict aGVHD in BMT with a partially T cell-depleted graft. We conclude, that HLA-identical siblings can be identified by means of serological typing for HLA-A and B and intermediate resolution molecular typing for DRB and DQB, but that for the prediction of aGVHD cellular tests with higher sensitivity and specificity as compared to the currently used HTLp-f and CTLp-f assays need to be developed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Base Sequence
  • Bone Marrow Transplantation / adverse effects*
  • Bone Marrow Transplantation / immunology*
  • Case-Control Studies
  • DNA Primers / genetics
  • Female
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / immunology
  • HLA Antigens
  • HLA-DP Antigens / genetics
  • HLA-DP beta-Chains
  • Histocompatibility Testing / methods
  • Humans
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Retrospective Studies
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • DNA Primers
  • HLA Antigens
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen