A new platelet alloantigen, Tu^a, on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia in two families

Abstract

We describe immunization of two mothers against a new platelet alloantigen, designated Tua, in association with thrombocytopenia in their first born children. The platelet-specific antibodies were identified by a glycoprotein-specific platelet protein assay with husband's platelets. Monoclonal antibodies against glycoprotein complex IIb/IIIa (AP2) and against glycoprotein IIb (SZ22) could be used to immobilize the antigen bearing protein. When monoclonal antibodies against glycoprotein Ib/IX (FMC25) or Ia/IIa (Gi9) were used, no platelet-specific antibodies were detectable. The previously described alloantigens on the glycoprotein IIb/IIIa complex (HPA 1,3,4, Sra and Vaa) were not responsible for the reaction. Immunochemical analysis by an immunoblot assay showed that the Tua antigen resides on GPIIIa but the antigen was destroyed by reduction of the protein. Altogether 10 individuals belonging to three unrelated families were shown to carry the antigen. The family studies within three generations indicated autosomal codominant inheritance. Thus the Tua antigen is apparently different from all previously published platelet alloantigens. One Tua positive blood donor was identified in a population study of approximately 150 individuals. This indicates a low frequency in the Finnish population. Extended population studies will be required to determine a more exact frequency of Tua antigen.

Genotype Frequencies of the Human Platelet Antigen, Ca/Tu, in Japanese, Determined by a PCR-RFLP Method

“…Eleven platelet-specific alloantigen systems have been reported to date, including HPA-1 to HPA-5, Ca/Tu, Mo, Sr", Nak", Va" and Gro" [3,[8][9][10][11][12][13]. According to gene analysis, the polymorphism in these eight platelet-specific alloantigens, except for Nak", Va" and Groa, was shown to be de rived from a single base pair substitution which led to a sin gle amino acid difference in the relevant glycoproteins [4,9,[14][15][16][17][18][19],…”

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

“…The requirement to identify such antibodies will vary according to patient populations. For example, although of relatively low frequency, a number of HPA 6bw-positive individuals and cases of anti-HPA-6bw causing FMAIT have already been identified in Finland [15,20]. To further validate the use of these peptides and define the incidence and importance of alloimmunization against the bw alleles of b3 in FMAIT, a larger number of clinical referrals must be tested in conjunction with additional negative control sera.…”

“…Sera containing alloantibodies against low frequency HPAs, HPA-6bw, -7bw, -8bw and -16bw and three for HPA-11bw, were provided by the laboratories which discovered the respective alloantigen, most of which have been described previously [10,[14][15][16][17][18][19][20]. Of the five anti-HPA-4a sera samples, A1 and A2 were from volunteer blood donors and the remainder were from FMAIT cases.…”

Severe Neonatal Alloimmune Thrombocytopenia due to& ;Anti-HPA-3a

“…The third cause (much less frequent) is HPA-3a alloimmunization. Other rare platelet-specific target antigens [10, 11, 12, 13, 14] have been also involved in NAIT.…”

“…In whites, the most common causes of NAIT are incompatibility in the platelet-specific HPA-1a (Pl A1 ) [1, 2, 3, 4, 5] and HPA-5b (Br a ) antigens [6, 7]. Other rare causes are alloantibodies such as HPA-3a (Bak a ) [1, 3, 5], HPA-4 [8, 9], or other newly described antibodies [10, 11, 12, 13, 14]. NAIT can lead to serious consequences such as central nervous system bleeding and death.…”