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

It has remained to be established that matching of the HLA-DP antigen plays a key role in bone marrow transplantation (BMT), mainly due to the difficulty of the primed lymphocyte test (PLT) method for DP typing. We previously reported an efficient technique for HLA class II genotyping, by digestion of polymerase chain reaction (PCR)-amplified genes with restriction fragment length polymorphisms (RFLP) endonucleases (PCR-RFLP method). DNAs from 46 recipients and corresponding donors in serologically HLA-identical sibling-BMT cases were DP typed by this PCR-RFLP method. Of the 46 cases, five (10.9%) were genetically DP mismatched (recombinant frequency between the DR-DQ and DP subregions was at least 2.7% per meiosis), providing an important opportunity to look at the effect of the disparity only seen in the DP antigen on BMT. Three of the four DP-mismatched BMT cases that could be evaluated developed severe acute graft-versus-host disease, suggesting that DP disparity played an important role in BMT.
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PMID:Severe acute graft-versus-host disease by HLA-DPB1 disparity in recombinant family of bone marrow transplantation between serologically HLA-identical siblings: an application of the polymerase chain reaction-restriction fragment length polymorphism method. 168 26

It has recently been reported that HLA-DP antigens may play an important role in the development of graft-versus-host disease (GVHD) following transplantations of haploidentical bone marrow as a treatment for haematological malignancies. Mixed lymphocyte culture (MLC) is routinely performed prior to bone marrow transplantation to assess the suitability of the donor, and we have therefore examined the role of HLA-DP in this test. One-way MLC chequerboard experiments were performed between 17 HLA-Dw3 homozygous typing cells (HTC) with a range of HLA-DP antigens represented, including HLA-DPw1, w2, w3, w4 and CP63. The experiments were performed on multiple occasions and each time a highly significant difference (P = less than 0.001) was observed between the Relative Responses (RR) in the HLA-DP matched responder/stimulator pairs and the HLA-DP mismatched pairs. There was, however, considerable overlap in these results with ranges in the HLA-DP-matched group RRs of 0-17%, and 0-62% in the mismatched group. Only 3.1% of the HLA-DP-matched grou had a RR greater than 5%, while 48% of the HLA-DP mismatched group had a RR greater than 5%. From these results it was calculated that a positive response (greater than 5%) has a 96% chance of being due to an HLA-DP disparity of one or two antigens. Conversely, with a negative MLC the chance of their being no HLA-DP antigen disparity was only 65%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An analysis of the effect of HLA-DP in the mixed lymphocyte reaction. 297 15

HLA-DP typing is not routinely performed before allogeneic BMT. This highly polymorphic class II locus is implicated in immune response and DP molecules may act as transplantation antigens. HLA-DP incompatibilities contribute to MCL. In BMT performed between siblings, HLA-DP mismatches are rare and the role of such incompatibility in GVHD is probably lower than minor histocompatibility antigen disparity. In unrelated BMT, the rate of HLA-DP mismatches is high and DP incompatibility cannot be used as an exclusion criterion in the selection of unrelated donors. Even if in vitro studies show that the HLA-DP antigen may be the target for GVHD, analysis of large numbers of unrelated BMT shows that DP incompatibility is not a risk factor for acute GVHD.
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PMID:HLA-DP and allogeneic bone marrow transplantation. 792 Feb 90