NAIT due to a presumably new alloantibody against Gp IIb

Background

Neonatal alloimmune thrombocytopenia (NAIT) is a disorder of the newborn due to fetomaternal incompatibility of platelet antigens. Polymorphisms associated with platelet alloimmunisation are primarily located in ITGB3 & ITGA2B. The latter one encodes for the α chain of Gp IIb/IIIa and to date, nine variants with corresponding alloantigens are known. The rare variant rs547581737 of ITGA2B (estimated frequency <10-4) leads to p.Arg774Trp. So far, no alloimmunisation is described for this variant.

Methods

Here, we present a case of a male newborn with a suspected NAIT and a presumably new alloantibody. Blood samples of all direct family members were analysed. Antibody detection was performed by indirect MAIPA (in-house assay). Serological analysis included a crossmatch between paternal platelets and maternal serum. Initial genotyping was performed by commercial SSP-PCR (BAGene HPA-TYPE, BAG Diagnostics). For sequencing of ITGA2B and ITGB3 a direct taq-cycle method was chosen.

Results

No maternal platelet specific alloantibody could be detected by indirect MAIPA using a routine platelet panel. For HPA-1, -2, -3, -4, -5, -6, -9, -15 systems, no incompatibility between mother and newborn was found by SSP genotyping. However, a crossmatch between maternal serum and paternal platelets was strongly positive (Gp IIb/IIIa). Thus, the existence of an antibody against a low-frequency antigen was assumed and sequencing of both eligible genes (ITGA2B and ITGB3) was initiated. The rare variant rs547581737 with a nucleotide exchange in exon 23 (c.C2320T) was found in the father and the newborn, but not in the mother. At GnomAD, an allele frequency of 4.6x10E-5 is given for this variant and no homozygote sample was found so far.

Conclusion

In Europeans, NAIT is caused by anti-HPA-1a in the majority of cases, though several cases with antibodies to low-frequency antigens have been described. Thus, the rare variant of ITGA2B in our case is probably also responsible for maternal alloimmunisation and neonatal thrombocytopenia. Further serological investigations are needed to prove this antibody specificity. However, our case demonstrates once again that a serological crossmatch is essential for detecting antibodies to novel antigens.

Offenlegung Interessenkonflikt:

All authors declare no conflicts of interest.