6 research outputs found
The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to Maternal ABO Genotypes
Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side
Anti-human platelet antigen-1α immunoglobulin G preparation intended to prevent fetal and neonatal alloimmune thrombocytopenia
Copyright: © 2016 Weng et al. This is an open
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DOI: 10.1371/journal.pone.0162973Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is
caused by maternal alloantibodies generated during pregnancy or at delivery as a result of
incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from
the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is
thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare
anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed.
Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization
against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the
supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography,
nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction
was characterized for purity and safety. PAK12 and quantitative monoclonal antibody
immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG.
Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments,
using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment
precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography
of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG
recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of
complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG
could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV
infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity
and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays
showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements opening perspectives
for the prevention of FNAIT