Study On Genetyping Of Human Platelet Alloantigen Systems

Alloantibodies against human platelet antigens (HPA) are involved inneonatal alloimmune hrombocytopenia, posttransfusion purpura andrefractoriness to random donor platelets [1]. The human platelet antigen (HPA)nomenclature system was adopted in 1990 by the ISBT platelet working party[2] to overcome problems with the previous nomenclature. Since then, a greaternumber of antigens have been described and the molecular basis of many hasbeen resolved [3]. To date, 24 platelet-specific alloantigens have been definedby immune sera, of which 12 are grouped in six biallelic systems (HPA-1, -2, -3,-4, -5, -15). For the remaining 12, alloantibodies against the thetical but not theantithetical antigen have been observed. The molecular basis of 22 of the 24serologically defined antigens has been resolved. In all but one of the 22, thedifference between self and non-self is defined by a single amino acidsubstitution generally caused by a single nucleotide polymorphism (SNP) inthegene encoding the relevant membrane glycoprotein. For the six biallelicHPA systems, SNP typing on large numbers of DNA samples has providedreliable information on allele frequencies, with significant differences occurringbetween populations [4]. The Platelet Nomenclature Committee (PNC) hasbeen created as a collaborative platform between the International Society ofBlood Transfusion (ISBT) platelet working party and the International Societyon Thrombosis and Haemostasis (ISTH) scientific subcommittee on plateletimmunology. This committee will be the guardian of the HPA nomenclaturesystem on behalf of the ISBT and the ISTH. Here we report on behalf of thePNC on the existence of three linked nomenclature tables to support thesystematic use of the HPA nomenclature in the clinical and scientificenvironments. When preparing these tables we made extensive use ofinternational databases containing information on the sequence of the humangenome. In addition, we also describe a formal process by which new HPAdesignations should be assigned under the control of the PNC. The content ofthis article has received approval from the relevant committees of the ISBT andISTH, and broad support from the wider Platelet Immunology community.HPA nomenclature: terminology and rules The HPA nomenclature aims tocategorize platelet-specific protein alloantigens. In this context, platelet-specificalloantigens are defined as all protein alloantigens expressed on the plateletmembrane, except those encoded by genes of the major histocompatibilitycomplex (MHC). An alloantigen is an antigen present in part of the population(as defined by the ability to detect it with a human immune serum) but absent inthe remainder of the same population. A plateletspecific alloantigen is called ahuman platelet antigen (or HPA) when its molecular basis has been defined.The different HPAs are grouped in systems based on having alloantibodiesdefining a given alloantigen and its 'antithetical' alloantigen. HPAs and theirsystems are numbered chronologically in order of the date of discovery (in thefuture: date of first submission to the PNC). The HPAs (and alleles) will bedesignated alphabetically in order of their frequency (from high to low) in theindex population. A 'w' designation is added after the antigen name if analloantibody against the antithetical antigen has not been reported.New antigens to be defined after the publication of this report will only beincluded in the HPA nomenclature table when approval from the PNC has beenobtained. Submissions should be made to the Secretary of the committee. ThePNC will take the following into account when considering their decision: (1)The genetic basis of the alloantigen must have been determined. Sequence datashould be supplied, preferably genomic DNA sequence or a minimum of cDNAsequence. (2) The association between the genetic mutation and the reactivity ofthe alloantibodies with the allelic forms of the protein must been shown inprotein-specific immunoassays. (3) At least two reference laboratories musthave con-firmed both the serological and molecular biology data. (4) Thecontributing laboratory (publishing authors) should provide data from apopulation study of the index population. A pedigree with typed individualsfrom the index family and/or other typed families would be of additional value.(5) The contributing laboratory should make all reasonable efforts to make ablood sample available to one of the repository laboratories for establishment ofa lymphoblastoid cell line. A flow chart for the steps involved in assignment ofa new HPA specificity by the PNC is shown.