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)

Cytotoxic T lymphocytes (CTL) specific for human minor histocompatibility (H) antigens can be isolated from the blood of major histocompatibility complex (MHC)-matched allogeneic bone marrow transplant (BMT) recipients and may play a prominent role in the graft-versus-host (GVH) and graft-versus-leukemia (GVL) reactions (Tsoi et al, J Immunol 125:2258, 1980; Tsoi et al, Transplant Proc 15:1484, 1983; Goulmy et al, Nature 302:159, 1983; Irle et al, Transplantation 40:329, 1985; and Niederwieser et al, Blood 81:2200, 1993). The identification of minor H antigens that are expressed in hematopoietic cells, including leukemic cells, but not in fibroblasts and other tissue types has suggested that such tissue-restricted antigens could potentially serve as targets for T-cell immunotherapy to enhance GVL activity without inducing GVH disease (de Bueger et al, J Immunol 149:1788, 1992; van der Harst et al, Blood 83:1060, 1994; and Dolstra et al, J Immunol 158:560, 1997). To explore the feasibility of this strategy, donor CD3+CD8+ CTL clones specific for recipient minor H antigens were isolated and characterized from allogeneic BMT recipients. CTL clones were obtained from the majority of donor/recipient pairs. Seventeen distinct minor H antigens distinguishable by their MHC-restricting allele, population frequency, and/or distribution of tissue expression were defined by 56 CD3+CD8+ CTL clones isolated from these patients. The MHC-restricting alleles for these CTL clones included HLA-A2 and HLA-B7, which had previously been shown to present minor H antigens to CTL, as well as HLA-A3, -A11, -B8, -B53, and -Cw7, which had not previously been described to present minor H antigens to CTL. Estimated phenotype frequencies for these 17 distinct minor H antigens range from 0.17 to 0.92. In vitro cytotoxicity assays using hematopoietic cells and fibroblasts as target cells showed that 5 of the 17 minor H antigens were expressed in both hematopoietic cells and fibroblasts. However, 12 were presented for CTL recognition only by hematopoietic cells and not by dermal fibroblasts derived from the same donors. These results significantly extend the spectrum of CTL-defined human minor H antigens that could potentially serve as target antigens for cellular immunotherapy to promote GVL activity after allogeneic BMT.
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PMID:Cytotoxic T-lymphocyte-defined human minor histocompatibility antigens with a restricted tissue distribution. 949 Jul 9

To clarify the effect of killer cell immunoglobulin-like receptor (KIR) ligand incompatibility on outcomes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients in complete remission after single cord blood transplantation (CBT), we assessed the outcomes of CBT registered in the Japan Society for Hematopoietic Cell Transplantation (JSHCT) database. A total of 643 acute leukemia (357 AML and 286 ALL) patient and donor pairs were categorized according to their KIR ligand incompatibility by determining whether or not they expressed HLA-C, Bw4 or A3/A11 by DNA typing. A total of 128 patient-donor pairs were KIR ligand-incompatible in the graft-versus-host (GVH) direction and 139 patient-donor pairs were incompatible in the host-versus-graft (HVG) direction. Univariate and multivariate analyses showed no significant differences between the KIR ligand-incompatible and compatible groups in the GVH direction for both AML and ALL patients of overall survival, disease-free survival, relapse incidence, non-relapse mortality and acute GVH disease. However, KIR incompatibility in the HVG direction ameliorated engraftment in ALL patients (hazard ratio 0.66, 95% confidence interval 0.47-0.91, P=0.013). Therefore, there were no effects of KIR ligand incompatibility in the GVH direction on single CBT outcomes for acute leukemia patients without anti-thymocyte globulin use. However, it is necessary to pay attention to KIR incompatibility in the HVG direction for engraftment.
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PMID:Effects of KIR ligand incompatibility on clinical outcomes of umbilical cord blood transplantation without ATG for acute leukemia in complete remission. 2429 16

In addition to T cells, NK cells can also participate in the outcome of hematopoietic stem cell transplantation (HSCT) mainly through the interaction between donor killer cell immunoglobulin-like receptors (KIRs) and recipient human leukocyte antigen (HLA) class I molecules. There is a risk of GVHD other than leukemia relapse after allogeneic HSCT that activation of donor NK cells in the absence of appropriate inhibitory ligands will be one of the reasons. To investigate the impact of donor KIRs and recipient KIR/HLA class I combinations on GVHD and leukemia relapse in patients with acute leukemia after HSCT, 100 patients with acute leukemia who received HSCT from their HLA-matched siblings were included in this study. Genotypes of 16 KIR genes and two 2DS4 variants (full length and deleted alleles), along with HLA-A/B genotypes, were determined by PCR-SSP. HLA-C genotyping was done with the SSO-Luminex method. Chimerism analysis was done using 16 short tandem repeats (STRs) to detect early leukemia relapse. Acute (a)GVHD occurred in 38 patients, and 16 of them died during the study. None of the recipients showed any sign of leukemia relapse after HSCT. Full donor chimerism was observed in all tested patients during the first year after HSCT. Our results also indicated an increased risk of aGVHD in AA recipients with the C2/Cx, Bw4+ (or A-Bw4+) or HLA-A3-/A11- genotypes who received HSCT from Bx donors. Our results showed that donor selection based on donor-recipient KIR genotypes and recipient HLA class I status can improve the outcome of HSCT.
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PMID:Impact of donor KIRs and recipient KIR/HLA class I combinations on GVHD in patients with acute leukemia after HLA-matched sibling HSCT. 3219 2