Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now possible to access more than one million HLA-A, B typed volunteer individuals willing to donate marrow and a preliminary search through the NMDP registry provides access to more than 200,000 HLA-A, B, DR typed donors. Fifty-four percent of preliminary searches yield at least one potentially HLA-matched donor but the majority of these successful searches involve patients of Caucasian origin. Substantially greater recruitment must occur among different racial and ethnic groups if minority patients are to have a better chance of finding an HLA match. This can be accomplished by recruiting diverse donors within each regional registry or by expanding worldwide the existing international registry network. Molecular typing and matching for alleles in the HLA-D region improve the precision of donor selection and the timeliness of the donor search process. Although the risk of GVHD in unrelated donor transplants remains higher than in HLA-identical sibling transplant is not as good as HLA-identical sibling transplants, newer methods of supportive care and GVHD control are providing and gradual improvement in both the safety of the procedure and long-term relapse-free survival.
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PMID:Marrow transplants from HLA matched unrelated donors: an NMDP update and the Seattle experience. 792 Feb 94

Functional studies of helper and cytotoxic T cells in families with recombinant HLA haplotypes have played a crucial role in the early studies of the HLA chromosomal region. It has been shown that for the generation of CTLs directed against HLA-A or -B antigen differences an additional difference in the HLA-D region between responder and stimulator cells was a prerequisite. We have re-examined in a sensitive limiting dilution assay the possibility of generating CTL against HLA class I antigens in responder-stimulator pairs with a negative MLC reaction of two recombinant families (differing in one or two HLA class I antigens but identical in class II antigens) and two pairs of unrelated individuals. In all cases we could detect low but definitely measurable CTL activity (8-15 CTL precursors in 10(6) PBMCs) directed against the mismatched class I HLA antigen(s). We conclude that mismatches in class I HLA antigens in MLC nonreactive responder-stimulator pairs can induce generation of allospecific CTLs. This has implications in allogeneic bone marrow transplantation with HLA-matched unrelated donors; i.e., in the case of an HLA-A,B,DR matched donor a low donor CTLpf against the recipient may be an indication of a serologically not-detected class I HLA "subtype" incompatibility which might cause graft-versus-host disease.
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PMID:Estimates of cytotoxic T-lymphocyte precursor frequencies against HLA class I antigens in responder-stimulator pairs with a negative mixed lymphocyte culture reaction. 884 34

The utility of the MLC assay as a test of HLA-D region matching and predictor of graft-versus-host disease (GvHD) was evaluated in 435 patients receiving marrow grafts from unrelated donors. Donors and recipients were phenotyped for HLA-A, B and DR antigens by serology, tested in MLC, and retrospectively genotyped for DRB1, B3, B4, B5, DQB1 and DPB1 alleles by PCR/SSOP. Of the 244 HLA-A, B, DR-identical donor-recipient pairs with valuable MLC and DRB1 typing results available, 208 were matched for HLA-A, B and DRB1, while 36 were matched for HLA-A and B and mismatched for a DRB1 allele. Donor anti-recipient relative responses (RR) in MLC, corresponding to the GvHD vector in marrow transplantation, ranged from 7.2 to 100%, with a median of 4.0%. A comparison of reactivity in MLC between pairs matched versus mismatched for DRB1 alleles showed a significant overlap in the distribution of RRs. Using optimally-defined RR cutoffs of 4 and 16%, no correlation between MLC results and risk of developing clinically significant grades III-IV GvHD (p=0.6 and 0.5, respectively) was found when the contribution of DRB1 mismatch was accounted for. Matching for DRB1 alleles, in contrast, was a better predictor of clinically significant GvHD, with DRB1-matched transplant recipients less likely to develop grades III-IV GvHD than DRB1-mismatched recipients (p=0.14). Among the 208 patients and donors matched for DRB1 alleles, the MLC, although reactive (RR > 4.0%) in 45% of cases, did not predict GvHD. Overall, these results underscore the limitations in using the MLC to predict DRB1 matching or risk of clinically significant GvHD among patients receiving unrelated marrow grafts. The availability of DRB1 allele matching by sequence-specific oligonucleotide probes (SSOP) or by direct sequencing provides a method for donor matching that is rapid, precise and superior to the MLC for predicting clinically relevant outcome.
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PMID:Evaluation of the mixed lymphocyte culture (MLC) assay as a method for selecting unrelated donors for marrow transplantation. 892 10


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