CD31 mismatching affects marrow transplantation outcome

Graft-versus-host disease (GVHD) complicating allogeneic bone marrow transp lantation (BMT) is often attributed to mismatched minor histocompatibility antigens (mHags), which are poorly defined in humans. CD31 is a candidate h uman mHag relevant to acute GVHD, but reports disagree about its level of s ignificance, the role of HLA restriction, and the relative importance of di fferent polymorphic codons within the molecule. We therefore examined in gr eater detail the impact of CD31-matching on BMT outcome in a prospective st udy from a single institution. Samples of recipient and donor DNA were coll ected pretransplantation. for all patients receiving unmanipulated bone mar row from an FILA-identical sibling over a 45-month period at our institutio n. CD31 DNA typing of alleles at the 3 polymorphic codons 125 (L or V), 563 (N or S), and 670 (R or G) was performed for 118 patient-donor pairs plus 2 additional pairs who had codon 125 typing only. Donor-recipient CD31 noni dentity was tested for correlation with BMT clinical outcome measures of se vere acute GVHD, chronic GVHD, relapse, and survival. Gene frequencies of a pproximately 0.5 for each allele at all 3 codons were comparable to previou s reports. Because complete association was seen for 563N with 670G and for 563S with 670R, nonidentity for those codons was analyzed as a single gene tic marker designated codon 563/670. Donor-recipient CD31 nonidentity was a significant risk factor for overall survival, both at codon 563/670 (hazar d ratio [hr] = 2.58, P = .005) and at codon 125 (hr = 1.07, P = .036). Simi lar results held for disease-free survival. Nonidentity at codon 563/670 wa s also a significant risk factor (odds ratio [OR] = 11.15, P = .011) for se vere (grades III, IV) versus no (grade 0) acute GVHD. Nonidentity at codon 125 posed less but still significant risk (OR = 9.30, P = .030). When the c omparison group without severe acute GVHD was expanded to include grade I a s well as grade 0 patients, the risk from CD31 nonidentity increased for bo th, codon 563/670 (OR = 12.31, P = .010) and codon 125 (OR = 11.24, P = .01 1). CD31 nonidentity remained a significant independent risk factor for sur vival and for severe acute GVHD when tested in multivariate analysis with t he covariates of adulthood, recipient-donor sex difference, ethnic group, d isease, pretransplantation risk category, HLA-A2 type, B44-like types, and GVHD prophylactic regimen. CD31 nonidentity showed a trend but failed to ac hieve statistical significance as a risk factor for relapse and for chronic GVHD. In conclusion, donor-recipient CD31 nonidentity is a significant ris k factor for survival and for severe acute GVHD in BLA-identical sibling BM T. The stronger associations with codon 563/670 suggest that polymorphism m ay be more important than the linked polymorphism at codon 125.