Donor CD31 genotype and its association with acute graft-versus-host disease in HLA identical sibling stem cell transplantation

Abstract

Summary:CD31 gene polymorphisms are implicated in the pathogenesis of graft-versus-host disease (GvHD) following haematopoietic stem cell transplantation (HST). We investigated the influence of CD31 genotype on the incidence of GvHD following HST from an human leukocyte antigen (HLA)-identical sibling donor. Donor and recipient CD31 codons 125, 563 and 670 DNA polymorphisms were determined in 85 cases of HLA identical sibling HST from two transplant centres. A correlation between CD31 genotype and acute GvHD was considered significant if observed in patients from both transplant centres independently. A strong correlation was identified between donor CD31 codon 125 genotype and the incidence of acute GvHD. Acute GvHD grades II-IV occurred in 27 of 46 (59%) recipients with a CD31 codon 125 leucine/valine heterozygous donor compared to nine of 39 (23%) recipients with a CD31 codon 125 homozygous donor (P ¼ 0.0019, relative-risk 2.45, 95% confidence interval 1.3-4.5). This correlation was significant in patients from both transplant centres (P ¼ 0.015 and P ¼ 0.019). We suggest that CD31 genotype may influence the function of donor-derived leukocytes and may be informative when there is a choice of comparable donors. Bone Marrow Transplantation (2005) 36, 151-156.

Primed T Cell Responses to Chemokines Are Regulated by the Immunoglobulin-Like Molecule CD31

“…CD31 polymorphisms affecting its binding site and cyoplasmic ITIMs correlate with increased GVHD and atherosclerosis severity [7], [8], [9], [10], [11], [12], [13]. It has been hypothesized that these mutations may influence CD31 binding affinity, structure and signalling capacity [36].…”

“…Loss of CD31 expression by CD4 + T cells correlates with increased size of atherosclerotic aortic aneurism size, a condition in which T cell immunity is a well-established pathogenic factor [5]. In addition, single nucleotide polymorphisms of CD31 encoding amino acid substitutions at positions affecting the binding site [6] and the intracellular ITIMs [7] are associated with increased severity of graft-versus-host disease after hematopoietic stem cell transplantation [8], [9], [10], [11], [12] and atherosclerosis [7], [13]. Although T cell-mediated inflammation contributes to the pathogenesis of both these conditions, the molecular mechanisms underlying this link are at present unclear.…”

CD31 signals confer immune privilege to the vascular endothelium

“…A few studies have described a link between the development of human atherosclerosis and the presence of CD31 SNPs. Interestingly, a number of the CD31 SNPs that have been associated with atherosclerosis (41)(42)(43)(44) are the same as those implicated in increased GVHD severity (45)(46)(47)(48)(49). The functional significance of these SNPs has yet to be explored, and their association with disease remains controversial (50).…”

NCI, NHLBI First International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Etiology and Pathogenesis of Late Effects after HCT Performed in Childhood—Methodologic Challenges

“…(33) A more recent British study found that disparity for CD31 polymorphisms did not associate with outcomes, but that genotype for SNP 125 was associated with risk of GvHD. (34) These authors suggest that the variant CD31 genotype had an effect on T-cell function. These papers, which include 15 years of work, offer no clarity regarding the clinical importance or mechanism of action of variants in a single gene, illustrating the complexity of translation of laboratory findings into clinical practice.…”