Incompatibility for CD31 and human platelet antigens and acute graft‐versus‐host disease after bone marrow transplantation

Abstract

Bone marrow transplantation (BMT) is often complicated by acute graft‐versus‐host disease (aGVHD). In patients transplanted with an HLA‐matched donor the occurrence of this complication is believed to be favoured by disparities at the minor histocompatibility antigens (mHA). However, few of these polymorphic molecules have been identified. We sought to determine whether donor/recipient incompatibility for HPA‐1, HPA‐2, HPA‐3, HPA‐5 or CD31 (codon 125) antigens represented a risk factor for aGVHD and genotyped these antigens in 70 bone marrow donors and their HLA‐identical recipients. All patients were children who received BMT for haematological malignancies at a single institution according to well‐defined therapy protocols. Statistical analysis showed that incompatibility for CD31 (codon 125) was a risk factor for grade II–IV aGVHD in the overall patient population, whereas HPA‐3 incompatibility predicted aGVHD occurrence in HLA‐A2 patients only. The magnitude of the aGVHD risk was directly related to the number of HPA/CD31 incompatibilities. No correlation was found between non‐identity for HPA/CD31 and aGVHD. Since incompatibility but not non‐identity for CD31 or HPA‐3 was a risk factor for aGVHD, we suggest that allelic variants of these molecules can serve as mHA in BMT recipients from HLA‐identical donors.

Low incidence of severe acute graft-versus-host disease in children given haematopoietic stem cell transplantation from unrelated donors prospectively matched for HLA class I and II alleles with high-resolution molecular typing

“…17,32,33 Both issues could be achieved by the use of functional assays. In this regard, promising results have been obtained with the use of the skin explant model, 34 whereas the frequency of alloreactive cytotoxic T-lymphocyte precursors, found to correlate with the incidence of acute GVHD in adults, 35 was not proved to be useful in paediatric patients.…”

“…16 In all cases, HLA class I (HLA-A, -B, -C) and class II (HLA-DRB1, -DQB1) loci were identified by polymerase chain reaction-single strand polymorphism (Dynal, Oslo, Norway) and sequence-based typing as previously described. 17 In all, 30 patient/donor pairs (48%) were considered fully compatible (10 out of 10 alleles matched). Among the other patients for whom a fully matched unrelated donor could not have been found, HSCT was performed despite the presence of one (n ¼ 22, 35%), two (n ¼ 9, 14%), or three (n ¼ 2, 3%) HLA antigen/ allele disparities.…”

Factors influencing post-transfusional platelet increment in pediatric patients given hematopoietic stem cell transplantation

“…15 Antibodies against HLA-class I antigens, glycoproteins (GP) IIb-IIIa, GPIb-IX and GPIa-IIa were investigated in serum samples by a solid-phase enzyme linked immunoadsorbant assay (PAK 2LE, GTI, Brookfield, WI, USA). To identify specificity of anti-GPIIb-IIIa (HPA-1, HPA-3 and HPA-4) or HLA-class I antibodies, a solid-phase antigen-capture enzyme-linked immunoadsorbant assay (PAK 1 and PRA QIIK-ID; GTI) was used.…”

“…Patients transplanted from an HLA-matched unrelated donor were treated, in addition to cyclosporin A, with a short course of methotrexate according to the schedule described by Storb et al, 14 together with either the monoclonal antibody Campath-1 G or anti-lymphocyte globulin, as previously reported. 15 Details of the clinical management after transplantation have been given elsewhere. 16 …”

“…Anti-HLA and platelet-specific antibodies were investigated before the conditioning regimen, at recovery from bone marrow aplasia following HSCT (days [15][16][17][18][19][20][21][22][23][24][25] and 40 days after HSCT. At the time of each platelet transfusion we also evaluated: body temperature (dichotomized as р37°C or Ͼ37°C), cytomegalovirus infection (defined as expression of the pp65 viral phosphoprotein on the leukocyte surface), 19 presence and severity of acute GVHD (classified according to Glucksberg et al 20 ), occurrence of thrombotic thrombocytopenic purpura (defined as microangiopathic hemolytic anemia with fragmentation of more than 5% of erythrocytes and no evidence of disseminated intravascular coagulation), occurrence of active mucosal bleeding (ie hematuria, blood in the stool, gum bleeding or epistaxis), spleen size (less or more than 1 cm below costal margin) or splenectomy before transplantation.…”