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)

Despite matching for serologically defined HLA-A, B, DR antigens, acute graft-versus-host disease (GVHD) is a major complication contributing to increased morbidity and mortality in patients who undergo marrow transplantation from unrelated donors. The extent to which unrecognized mismatching for alleles that encode DR1-DR18 contribute to the increased risk of acute GVHD and overall survival is unknown. We analyzed 364 patients and their HLA-A, B, DR serologically matched donors to determine whether molecular typing of DRB1 alleles can allow more accurate donor/recipient matching and thereby improve clinical outcome after marrow transplantation. DRB1 alleles were typed by sequence-specific oligonucleotide probe hybridization methods. Selected alleles were confirmed by DNA sequencing. Of the 364 pairs, 305 were matched and 59 were mismatched for DRB1. The probability of moderate to severe acute GVHD was .48 for the matched and .70 for the mismatched patients. Compared with mismatched patients, the estimated relative risk (RR) of GVHD for matched patients was .58 (95% confidence interval [CI], .40 to .85). DRB1 matching decreased the risk of transplant-related mortality (RR, .66; 95% CI, .44 to .97) and was associated with decreased overall mortality (RR, .71; 95% CI, .51 to 1.0). Therefore, matching DRB1 alleles of the donor and recipient decreases the risk of acute GVHD and improves survival after unrelated marrow transplantation. These results indicate that prospective matching of patients and donors for DRB1 alleles is warranted.
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PMID:The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation. 763 70

HIV induces disease only following chronic activation of the immune system. Other retroviruses such as the mouse mammary tumour virus (MMTV) activate a large percentage of T cells by encoding a superantigen (SAg). To date there is no evidence that HIV encodes a SAg. An alternative way to induce pan-activation of the immune system is by allogeneic stimulation, which occurs following transplantation. Here we extend previous work which demonstrated that HIVpg120 could bind peptides in a similar manner to HLA, by demonstrating that human antigen presenting cells (APCs) expressing gp120 (but not DR1) can present a DR1-restricted peptide to induce proliferation of a DR1-restricted peptide-specific T-cell line in a similar manner to the same peptide presented by a DR1 expressing APC. Our data provide strong support for the hypothesis that the HLA-like regions of gp120 encode functional properties shared with HLA, and could explain the extraordinary clinical and immunological similarities between AIDS and chronic graft versus host disease.
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PMID:HIV gp120 plus specific peptides are recognized in a similar manner to specific HLA plus peptide by HLA-restricted antigen-specific T-cell lines. 1073 64

Frequencies of human leucocyte antigens (HLA)-A, -B and -DR were determined in 751 patients with chronic myelogenous leukaemia (CML) reported to the European Group for Blood and Marrow Transplantation after bone marrow transplantation from HLA-identical family donors and related to the occurrence of graft-versus-host disease (GVHD). HLA-A3 and DR1 were significantly associated with acute GVHD, the first with a higher risk (44% in HLA-A3(+) versus 34% in HLA-A3(-) patients) and the latter with a lower risk (28% in HLA-DR1(+) versus 38% in HLA-DR1(-) patients) for developing acute GVHD grade II--IV. Both factors were independent of known variables for GVHD as shown in a multivariate analysis. The results show that MHC alleles independently influence the incidence of GVHD in bone marrow transplantation from an HLA-identical donor for first chronic-phase CML. Possible mechanisms might include an HLA antigen-specific allele-associated effect, and/or non-specific allele-associated immune hypo- or hyper-responsiveness.
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PMID:HLA-A3 increases and HLA-DR1 decreases the risk of acute graft-versus-host disease after HLA-matched sibling bone marrow transplantation for chronic myelogenous leukaemia. 1147 42

The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope-binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Single mismatched alleles were categorized into six HLA-A (A01, A01A03, A01A24, A02, A03, A24), six HLA-B (B07, B08, B27, B44, B58, B62), two HLA-C (C1, C2), and five HLA-DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Supertype B mismatch was associated with increased risk of grade II-IV acute graft-versus-host disease (hazard ratio =1.78, P=0.0025) compared to supertype B match. Supertype B07-B44 mismatch was associated with a higher incidence of both grade II-IV (hazard ratio=3.11, P=0.002) and III-IV (hazard ratio=3.15, P=0.01) acute graft-versus-host disease. No significant associations were detected between supertype-matched versus -mismatched groups at other HLA loci. These data suggest that avoiding HLA-B supertype mismatches can mitigate the risk of grade II-IV acute graft-versus-host disease in 7/8-mismatched unrelated donor hematopoietic cell transplantation when multiple HLA-B supertype-matched donors are available. Future studies are needed to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation.
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PMID:Human leukocyte antigen supertype matching after myeloablative hematopoietic cell transplantation with 7/8 matched unrelated donor allografts: a report from the Center for International Blood and Marrow Transplant Research. 2724 20