Polymorphism of adhesion molecule CD31 and its association with graft vs. host disease (GVHD)

Polymorphism of adhesion molecule CD31 and its association with graft vs. host disease (GVHD)

2:00 p.m.-3:30 p.m. 32 IIAbstract Presentations 1O~ 6.2 POLYMORPHISM OF ADHESION MOLECULE CD31 AND ITS ASSOCIATION WITH GRAFT VS. HOST DISEASE (GV...

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2:00 p.m.-3:30 p.m.

32

IIAbstract Presentations 1O~

6.2

POLYMORPHISM OF ADHESION MOLECULE CD31 AND ITS ASSOCIATION WITH GRAFT VS. HOST DISEASE (GVHD). E Behar, N Chao, D Hiraki, S Krishnaswamy, J Zehnder, FC Grumet. Departments of Pathology and Medicine, Stanford University, Stanford, CA. Little is known about clinically significant human minor histocompatibility genes and their alloantigens. Limitations of alloantibody or cell mediated techniques to characterize such alloantigens led us to try direct DNA sequencing to identify relevant new polymorphisms. Because of the tissue distribution [e.g., expression on vascular endothelial cells (VEC)] and possible heterogeneity of CD31, this molecule was selected as a model candidate for a minor locus transplant antigen. RNA's extracted from VEC or PBL of 21 random persons were reverse transcribed and target segments were PCR amplified for direct heterozygous sequencing with T7 polymerase on an ALF automated sequencer. The only observed polymorphism was a frequent C.TG/QTG substitution at codon-125 resulting in a LeuN al diallelism (designated CD31.L and CD31.V). Sequence specific primers (SSP) were designed and 142 additional random individuals were PCR-SSP typed. Total phenotype frequencies of CD31.L (0.30), CD31.V(0.28) and CD31.LlCD31.Y (0.42) were a good fit for Hardy Weinberg equilibrium. Differential immunoreactivity ofCD31.L vs. CD31.V was shown in F ACS by selective binding to VEC of different anti-CD31 monoclonal antibodies. Clinical relevance of the CD31 polymorphism was tested in patients transplanted with bone marrow from HLA matched siblings. CD31 allele matching was present in 12/12 patients with No GVHD, but in only 2/8 patients with Acute GVHD (p = .0007). We conclude: a) This is the first clearly defined polymorphism of human adhesion molecules, and b) CD31 represents a significant new transplantation alloantigen.

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HLA CLASS I MATCHING AND UNFELATED DONOR BONE MARROW TRANSPLANTION. I Scott, M Bunce, P Brookes, R Arguello, J O'Shea, J-M Tiercy, R Lechler, J.M Goldman, 1.A Madri2al, The Anthony Nolan Research Centre, UK; The Oxford Transplantation Centre, UK, Hospital Cantonal Universitaire, Switzerland; The Royal Postgraduate Medical School, UK. Despite the import.'\1lce of HLA compatibility for unrelated donor bone marrow transplantation (BMT) most class I typing strategies are unable to identify many potential discrepancies. Cellular and molecular techniques have been employed in an attempt to resolve this problem. Using a limiting dilution assay the patient-specific donor CTL precursor frequencies were measured in 260 patient/potential donor pairs previously typed by serology for class I and DNA-based typing for class II. AnalySis of correlation of detected HLA-A and -B mismatches with high CTLp frequencies (>1:100,000) was found to be highly significant (p
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