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)

HLA incompatibility between bone marrow recipient and unrelated donor pairs is often associated with severe acute graft-versus-host disease following bone marrow transplantation. Due to the extensive polymorphism of HLA genes, finding genotypically identical pairs is a difficult challenge. Therefore, it is crucial to single out the relevance of each HLA gene and, within each sequence, the polymorphic positions that induce a T-cell response. Among HLA class II genes, the relevance of HLA-DPB1 in inducing graft-versus-host disease is still controversial. In this study, we selected 37 bone marrow transplant pairs on the basis of HLA class I A and B identity as determined by isoelectric focusing and of class II identity as determined by serology and by low-resolution genomic typing. We analyzed them for the possible relationship between frequency of cytotoxic T lymphocyte and helper T lymphocyte precursors (CTLp and HTLp, respectively) and genomically determined class II mismatches. Seventeen pairs had high numbers of both CTLp and HTLp. They were not further considered because of the difficulty in determining whether the T-cell response was induced by class I or class II mismatches. Of the remaining pairs with low CTLp and high HTLp, six had disparities at HLA-DRB1 and HLA-DPB1 genes, and 14 differed only at the HLA-DPB1 locus. Among the latter pairs, we found a correlation between HLA-DPB1 mismatches and HTLp frequency, thus suggesting that disparity at this locus influences the alloreactive T-cell response. When the HTLp frequency was correlated with each single mismatch found in the 14 pairs, it appeared that the nature of the amino acid at position beta69 played a relevant role in inducing alloreactivity.
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PMID:HLA-DPB1 mismatch at position 69 is associated with high helper T lymphocyte precursor frequencies in unrelated bone marrow transplant pairs. 893 83

The modified mixed leukocyte reaction (MMLR) test consists of the standard MLR (SMLR) test to which interleukin-4 (IL-4) has been added. It is a sensitive procedure capable of detecting alloreactivity not detected by the SMLR. In the present study we applied the MMLR test to unrelated bone marrow transplantation (BMT) in an attempt to predict graft versus host disease (GVHD) and graft rejection (GR) by detecting alloreactivity between recipient/donor pairs otherwise found to be fully matched (HLA class I A and B tested by serology; class II DRB1 and DQB1 by sequence specific oligonucleotide probes [SSOP]) and by studying the relationship of MMLR alloreactivity and HLA-C disparity in the prediction of transplant related complications. Thirty-five patients transplanted from unrelated donors were included in the study. The MMLR test was seen to correlate with the incidence of transplant related complications, as of the 19 positive, cases 12 (63%) developed acute GVHD and 7 (37%) GR, while of the 16 negative cases only 5 (31%) developed GVHD (4 acute, 1 chronic) (p = 0.0001) and 2 (12.5%) GR. No such correlation was seen between the SMLR and the incidence of transplant related complications: the SMLR test was positive in only 4 (11%) cases (all of which developed GVHD or GR) but of the 31 negative cases 22 (71%) also developed GVHD or GR. Reactivity in the MMLR also correlated with molecular HLA-C disparity (p = 0.015): While of the 19 positive cases 10 (53%) had molecular HLA-C disparity, of the 16 cases with negative MMLR, 14 (87.5%) were matched for molecular HLA-C. Two-way analysis confirmed that patients with positive MMLR transplanted from HLA-C mismatched donors were more likely to develop post BMT complications, including GVHD and GR, than patients with negative MMLR transplanted from HLA-C matched donors (r = +0.70) (p = 0.001). We conclude that the MMLR test may be a useful tool in the prediction of transplant related complications such as GVHD and GR, post unrelated BMT. Moreover, the MMLR test, in conjunction with molecular HLA-C typing, may improve unrelated donor selection.
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PMID:Positivity in a modified mixed leukocyte reaction test correlates with molecular HLA-C disparity in prediction of unrelated bone marrow transplantation outcome. 1052 90