HLA‐DRB3*01:01 is a predictor of immunization against human platelet antigen‐1a but not of the severity of fetal and neonatal alloimmune thrombocytopenia

Abstract

In contrast to HLA-DRB4*01:01P, the inheritance of HLA-DRB3*01:01 is strongly associated with the propensity for mounting a humoral immune response against fetal HPA-1a antigen. Neither a homozygous nor a compound heterozygous gene dose predicts the severity of the disease. Testing for the presence of HLA-DRB3*01:01 might be very useful in counseling women at risk of FNAIT due to anti-HPA-1a.

Risk of HPA‐1a–immunization in HPA‐1a–negative women after giving birth to an HPA‐1a–positive child

“…Thus, it is highly likely that this selection of samples is biased toward more severe FNAIT cases. The fact that only 1.9% of the women in their population were HLA‐DRB3*01:01–negative, as opposed to 7.9% in the study by Kjeldsen‐Kragh et al and 28% in the study by Turner et al confirms that the population studied by Wienzek‐Lischka et al is biased toward the more severe cases. Also, Wienzek‐Lischka et al did not include nullizygous, but only hetero−/hemizygous and homozygous in their analysis, as opposed to the study by Titze et al Consequently, the selection bias may have prevented Wienzek‐Lischka et al from detecting an effect of the HLA‐DRB3*01:01 zygosity status on neonatal platelet count.…”

“…None of these 19 women gave birth to a child with severe thrombocytopenia (platelet count <50 × 10 9 /L). The view that close clinical follow‐up may be not necessary for HLA‐DRB3*01:01–negative women has also recently been suggested by the platelet immunology group in Gießen, Germany …”

“…The opposite trend was seen with regard to neonatal platelet counts: HPA-1a-immunized women negative for HLA-DRB3*01:01 give birth to children with normal platelet counts or occasionally moderately reduced platelets counts usually without clinical consequences, whereas newborns of women carrying one copy of this allele have lower platelet counts and women homozygous for HLA-DRB3*01:01 give birth to children with the most severe thrombocytopenia. 29 Wienzek-Lischka et al 30 have also examined if there is a difference in neonatal platelet count in children born of women who have one or two doses of HLA-DRB3*01:01, and reached the conclusion that the neonatal platelet count is not different between these two groups. The population examined by Wienzek-Lischka et al 30 originated from mother-child samples that were referred to their reference laboratory due to suspicion of FNAIT.…”

“…The view that close clinical follow-up may be not necessary for HLA-DRB3*01:01-negative women has also recently been suggested by the platelet immunology group in Gießen, Germany. 30 Implementing FNAIT screening could also be accomplished by HPA-1a typing followed by screening for HPA-1a antibodies in HPA-1a-negative women every trimester through pregnancy. This approach is used by some centers when a woman is serendipitously identified to be HPA-1a-negative and becomes pregnant with an HPA-1a-positive fetus.…”

Investigations for fetal and neonatal alloimmune thrombocytopenia: communication from the SSC of the ISTH

“…glycoprotein‐specific assays such as MAIPA or MACE and a whole‐platelet assay such as platelet adhesion or suspension immunofluorescence tests) for alloantibody detection will reduce the risk of false‐negative tests. Nevertheless, a discrepancy exists between HPA‐1a incompatibility and antibody formation because immunization is dependent on other factors, including the HLA‐DRB3*0101 genotype .…”