Three Cases of Platelet Alloimmunisation Associated with the Presence of a Novel Platelet-Specific Antibody

Abstract

Background and Objectives: In three cases of platelet alloimmunisation, a platelet-specific alloantibody was detected which could not be classified within the known human platelet alloantigen or HLA systems. The first case was of a family in which two siblings suffered neonatal alloimmune thrombocytopenia at birth. In the second case, the newborn was suffering from phocomelia with hypoplastic thrombocytopenia. The third case was a male who became refractory to transfusions of HLA-matched platelets after a related bone marrow transplantation. Materials and Methods: The serum samples were investigated by: enzyme-linked immunosorbent assay, platelet suspension immunofluorescence test (PSIFT), monoclonal antibody immobilisation of platelet antigens assay (MAIPA), and by the lymphocytotoxicity test. Results: The antibody gave positive reactions with 26% of normal donor platelets. Surprisingly, no platelet-specific antibody was detected by PSIFT or by MAIPA and there was no evidence found to support classifying the antibody within the HLA system. Conclusion: The reactivity pattern of the antibody detected and the clinical presentation of the three cases described, strongly suggest the presence of an additional platelet-specific alloantigen system.

A modified rapid monoclonal antibody‐specific immobilization of platelet antigen assay for the detection of human platelet antigen (HPA) antibodies: a multicentre evaluation

“…Clinical samples typically referred to a platelet immunology laboratory were used in the second phase of the assessment of the MR‐MAIPA. The characteristics of the 61 blinded samples are presented in Table 3, with 49 samples containing HPA antibodies, a unique sample with anti‐Mou a [17], five with panreactive GP antibodies, one that reacted in the PIFT only, two with HLA antibodies only (no platelet‐specific antibodies) and three inert samples. Testing of the 61 blinded samples by a single operator (KC) in the Cambridge laboratory on two occasions with two different but partially overlapping sets of capture mAbs (RFGP56, NBS‐P16, CLB‐MB45 and W6/32 vs. NBS‐PAB‐1, NBS‐PAB‐6, NBS‐5B12, NBS‐P16, NBS‐PAB‐5 and W6/32) showed complete concordance between the two tests with positive results for all but two of the 58 samples with platelet antibodies and no significant signal with the three inert samples (data not shown).…”

A single‐nucleotide polymorphism in the human ITGB3 gene is associated with the platelet‐specific alloantigen Vaa (HPA‐17bw) involved in fetal maternal alloimmune thrombocytopenia

“…The ITGA2B and ITGB3 genes are polymorphic and harbor 11 nsSNPs, which are at the basis of different HPAs 7 . The Va a PLT‐specific alloantigen is one of two remaining antigens that have been defined by serologic means but have yet to be characterized at the genetic or molecular level 8,9 . The aim of this study was to identify the molecular nature of Va a .…”

“…In addition, if the alloantibody against the antithetical antigen remains to be reported, a “w” designation is added after the name of the antigen as illustrated by the low‐frequency HPAs, −6bw to −16bw listed in the Immuno Polymorphism Database (http://www.ebi.ac.uk/ipd/hpa/). 7 The genetic basis of two serologically defined PLT‐specific antigens, which remains undetermined, include Va a , 8 and the case described by Masters and Taaning 9 . We detected the Va a antibody by testing maternal serum against paternal PLTs by the monoclonal antibody immobilization of PLT antigen (MAIPA) assay, which demonstrated that the antigen is carried on αIIbβ3 4,5,8 .…”

Three novel β3 domain-deletion peptides for the sensitive and specific detection of HPA-4 and six low frequency β3-HPA antibodies

“…Twelve additional alloantigens encoded by rare alleles of the genes encoding immunogenic platelet membrane glycoproteins have been identified [3]. For all but two [8,9], the genetic basis has been resolved and HPA‐bw status has been assigned; as to date, antibodies against the antithetical HPA‐a antigens have yet to be reported. The MAF for all is assumed to be extremely low, with estimates ranging from 0.001 and 0.05, but reliable data are lacking for most sequence variants [7,10,11].…”

“…Eight of the rare nsSNPs are in the ITGB3 gene, all in the background of the ITGB3*001 sequence haplotype, and three reside in ITGA2B , GP1BB and ITGA2 genes. The molecular basis of the potential additional novel antigen implicated by the report of Masters and Taaning remains undetermined [3,9].…”