New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia

Peterson, Julie A.; Pechauer, Shannon M.; Gitter, M.; Kanack, Adam; Curtis, Brian R.; Reese, Jeff; Kamath, Vasudeva M.; McFarland, Janice G.; Aster, Richard H.

doi:10.1111/j.1537-2995.2011.03428.x

Cited by 29 publications

(27 citation statements)

References 45 publications

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“…DNA-based platelet typing [2] confirmed that the patient’s genotype was HPA-1b/b, HPA-2b/b, a combination found in about one in 2,500 African-Americans.…”

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confidence: 99%

An unexpected development after surgery—post‐transfusion purpura!

et al. 2016

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“…DNA-based platelet typing [2] confirmed that the patient’s genotype was HPA-1b/b, HPA-2b/b, a combination found in about one in 2,500 African-Americans.…”

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confidence: 99%

An unexpected development after surgery—post‐transfusion purpura!

et al. 2016

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“…Diagnosis of NAIT was considered to be confirmed when a maternal antibody was identified that recognized an HPA present in the father or, in rare cases, was specific for GPIV (CD36); other cases were considered to be “unresolved.” Detailed clinical information was available only on cases in which a paternal LFHPA antigen was identified in the Phase 1 study; histories in these cases were consistent with NAIT of varying degrees of severity. Some cases in which LFHPAs were identified in the Phase 1 study (see Results) have been described previously in a different context …”

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confidence: 53%

Low‐frequency human platelet antigens as triggers for neonatal alloimmune thrombocytopenia

et al. 2013

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Background Twenty-four low frequency platelet antigens (HPAs) have been implicated as immunogens in neonatal alloimmune thrombocytopenia (NAIT). We performed studies to define more fully how often these antigens trigger maternal immunization leading to NAIT. Study design and methods In a Phase 1 study, fathers of selected NAIT cases not resolved by serologic testing but thought to have a high likelihood of NAIT on clinical and serologic grounds were typed for low frequency HPAs (LFHPAs) by DNA sequencing. In a Phase 2 study, high-throughput methods were used to type fathers of 1067 consecutive unresolved NAIT cases for LFHPAs. Mothers of 1338 unresolved cases were also typed to assess the prevalence of LFHPAs in a population racially/ethnically similar to the fathers. Results In Phase 1, LFHPAs were identified in 16 of 244 fathers (6.55%). In Phase 2, LFPAs were found in only 28 of 1067 fathers (2.62%). LFHPAs were identified in 27 of 1338 maternal samples (2.01%). HPA-9bw was by far the most common LFHPA identified in the populations studied and was the only LFHPA that was significantly more common in fathers than in mothers of affected infants (P=0.02). Conclusions Maternal immunization against recognized LFHPAs accounts for only a small fraction of the cases of apparent NAIT not resolved by standard serologic testing. Typing of the fathers of such cases for LFHPAs is likely to be rewarding only when a maternal antibody specific for a paternal platelet glycoprotein is demonstrated and/or there is compelling clinical evidence for NAIT.

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“…MACE was carried out as described previously 28 . In brief, HEK293 cell lines stably expressing recombinant human CTL2-GFP (R154 or Q154) were sensitized with human HNA-3a antibodies (diluted 1:5), washed and lysed with 1.0% Triton X-100.…”

Section: Methodsmentioning

confidence: 99%

Transfusion‐related acute lung injury–associated HNA‐3a antibodies recognize complex determinants on choline transporter‐like protein 2

et al. 2014

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Background HNA-3a specific antibodies can cause severe, sometimes fatal, transfusion related acute lung injury (TRALI) when present in transfused blood. The HNA3-a/b antigens are determined by an R154Q polymorphism in the first of five extracellular loops of the 10-membrane spanning choline transporter-like protein 2 (CTL2) expressed on neutrophils, lymphocytes and other tissues. About 50% of HNA-3a antibodies (Type 1) can be detected using CTL2 Loop 1 peptides containing R154; the remaining 50% (Type 2) fail to recognize this target. Understanding the basis for this difference could guide efforts to develop practical assays to screen blood donors for HNA-3 antibodies. Study design and methods Reactions of HNA-3a antibodies against recombinant versions of human, mouse, and human/mouse (chimeric) CTL2 were characterized using flow cytometry and various solid phase assays. Results Findings made show that, for binding to CTL2, Type 2 HNA-3a antibodies require non-polymorphic amino acid residues in the third, and possibly the second, extracellular loops of CTL2 to be in a configuration comparable to that found naturally in the cell membrane. In contrast, Type 1 antibodies require only peptides from the first extracellular loop that contain R154 for recognition. Conclusion Although Type 1 HNA-3a antibodies can readily be detected in solid phase assays that use a CTL2 peptide containing R154 as a target, development of a practical test to screen blood donors for Type 2 antibodies will pose a serious technical challenge because of the complex nature of the epitope(s) recognized by this antibody sub-group.

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New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia

Cited by 29 publications

References 45 publications

An unexpected development after surgery—post‐transfusion purpura!

An unexpected development after surgery—post‐transfusion purpura!

Low‐frequency human platelet antigens as triggers for neonatal alloimmune thrombocytopenia

Transfusion‐related acute lung injury–associated HNA‐3a antibodies recognize complex determinants on choline transporter‐like protein 2

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