title: 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.
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.
authors.affiliation: Blood Transfusion Service, University Hospital Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van der Meer
authors.forename: W A
authors.initials: WA
authors.lastname: Allebes
authors.forename: C E
authors.initials: CE
authors.lastname: Voorter
authors.forename: E M
authors.initials: EM
authors.lastname: van den Berg-Loonen
authors.forename: A V
authors.initials: AV
authors.lastname: Schattenberg
authors.forename: T J
authors.initials: TJ
authors.lastname: de Witte
authors.forename: I
authors.initials: I
authors.lastname: Joosten
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology*; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D006680:HLA Antigens; D006682:HLA-DP Antigens / Q000235:genetics; D059868:HLA-DP beta-Chains; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D017931:DNA Primers; D006680:HLA Antigens; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen