Diagnosis and Management of Neonatal Alloimmune Thrombocytopenia

Arnold, Donald M.; Smith, James W.; Kelton, John G.

doi:10.1016/j.tmrv.2008.05.003

Cited by 59 publications

(75 citation statements)

References 87 publications

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“…1 Mismatch between fetal and maternal platelet antigens can lead to the production of maternal immunoglobulin G anti-HPA-1a alloantibodies that cross the placenta and cause thrombocytopenia in an HPA-1a-positive fetus. 2,3 Approximately 2% of white women are HPA-1b homozygous, and 10% of these develop anti-HPA-1a alloantibodies during pregnancy. 2,3 The estimated incidence of severe neonatal alloimmune thrombocytopenia (NAIT) is approximately 1 in 1100 neonates, and the clinical manifestations range from mild purpura to intracranial hemorrhage.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 Approximately 2% of white women are HPA-1b homozygous, and 10% of these develop anti-HPA-1a alloantibodies during pregnancy. 2,3 The estimated incidence of severe neonatal alloimmune thrombocytopenia (NAIT) is approximately 1 in 1100 neonates, and the clinical manifestations range from mild purpura to intracranial hemorrhage. 2,3 Maternal responsiveness to HPA-1a shows strong associations with major histocompatibility complex class II, with greater than 95% of responders carrying the DRB3*0101 allele encoding human histocompatibility leukocyte antigen (HLA)-DR52a, 4,5 and up to 94% may carry the DQB1*02 allele.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 The estimated incidence of severe neonatal alloimmune thrombocytopenia (NAIT) is approximately 1 in 1100 neonates, and the clinical manifestations range from mild purpura to intracranial hemorrhage. 2,3 Maternal responsiveness to HPA-1a shows strong associations with major histocompatibility complex class II, with greater than 95% of responders carrying the DRB3*0101 allele encoding human histocompatibility leukocyte antigen (HLA)-DR52a, 4,5 and up to 94% may carry the DQB1*02 allele. 6 Classical immunoglobulin G antibody responses are dependent on T-helper (Th) cells that recognize antigen as short, processed, linear peptides bound to major histocompatibility complex molecules on antigen-presenting cells (APCs).…”

Section: Introductionmentioning

confidence: 99%

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Naturally processed peptides spanning the HPA-1a polymorphism are efficiently generated and displayed from platelet glycoprotein by HLA-DRB3*0101–positive antigen-presenting cells

Sarab

Moss

Barker

et al. 2009

Blood

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IntroductionHuman platelet antigen (HPA)-1a and HPA-1b alloantigens are determined, respectively, by the polymorphism Leu or Pro at position 33 of the ␤ 3 chain (glycoprotein IIIa [GPIIIa]) of the platelet integrin ␣ IIb ␤ 3 . 1 Mismatch between fetal and maternal platelet antigens can lead to the production of maternal immunoglobulin G anti-HPA-1a alloantibodies that cross the placenta and cause thrombocytopenia in an HPA-1a-positive fetus. 2,3 Approximately 2% of white women are HPA-1b homozygous, and 10% of these develop anti-HPA-1a alloantibodies during pregnancy. 2,3 The estimated incidence of severe neonatal alloimmune thrombocytopenia (NAIT) is approximately 1 in 1100 neonates, and the clinical manifestations range from mild purpura to intracranial hemorrhage. 2,3 Maternal responsiveness to HPA-1a shows strong associations with major histocompatibility complex class II, with greater than 95% of responders carrying the DRB3*0101 allele encoding human histocompatibility leukocyte antigen (HLA)-DR52a, 4,5 and up to 94% may carry the DQB1*02 allele. 6 Classical immunoglobulin G antibody responses are dependent on T-helper (Th) cells that recognize antigen as short, processed, linear peptides bound to major histocompatibility complex molecules on antigen-presenting cells (APCs). The identification of the immunodominant helper epitopes on the integrin sequence containing the HPA-1a polymorphic site would be an important step toward understanding and controlling the immune response to HPA-1a. Earlier studies have shown that short, synthetic HPA-1a peptides containing the Leu 33 polymorphism bind to recombinant DR52a molecules, whereas the Pro 33 version does not, with Trp 25 and Leu 33 predicted to be important anchor residues. 7 The dominant synthetic HPA-1a peptides recognized by peripheral blood Th cells from women alloimmunized with anti-HPA-1a contain the Trp 25 -Leu 33 core sequence, with Leu 33 preferentially at the C-terminus. 8 Recent characterization of the fine specificity of Th cell clones derived from women with NAIT also mapped a putative core epitope spanning Trp 25 -Leu 33 . 9 However, antigen processing within APCs is highly selective, with very few peptides typically generated from any given protein for efficient display to Th cells, 10-13 and there is no direct evidence that this core sequence is indeed presented from platelet glycoprotein. The aim of this study was therefore to determine whether DRB3*0101 homozygous APCs, pulsed with HPA-1a, naturally process and present peptides spanning the predicted Trp 25 -Leu 33 core epitope. Methods Antigen preparationDNA encoding HPA-1a amino acids 1-62 was cloned into the expression vector pGEX-6P-1, and Escherichia coli BL21(DE3) cells were transformed. This sequence corresponds to the complete plexin-semaphorinintegrin (PSI) domain of platelet GPIIIa, which spans the Leu 33 HPA-1a polymorphism and expresses the HPA-1a antigen. 14 Because the PSI domain is predicted to be on the exterior of the GPIIIa protein 14 and accessible to processing enzymes, ...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Naturally processed peptides spanning the HPA-1a polymorphism are efficiently generated and displayed from platelet glycoprotein by HLA-DRB3*0101–positive antigen-presenting cells

Sarab

Moss

Barker

et al. 2009

Blood

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“…Still, signs consistent with moderate to severe thrombocytopenia, including petechiae, bruising and bleeding, can be present. Although skin bleeding may occur in almost half of the cases, intracranial haemorrhage is the most serious complication, present in about 8–22% of affected newborns, occurring in utero in 50–80% of cases 1–4…”

Section: Introductionmentioning

confidence: 99%

“…Adequate platelet counts should be assured in the first 3–4 days lowering the risk of intracranial haemorrhage. Intravenous immunoglobulin (IVIG) and methylprednisolone are used as adjunctive therapy 1 4…”

Section: Introductionmentioning

confidence: 99%