A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Killie, Mette Kjær; Husebekk, Anne; Kjeldsen‐Kragh, Jens; Skogen, Bjøŕn

doi:10.3324/haematol.12515

Cited by 131 publications

(130 citation statements)

References 26 publications

(38 reference statements)

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“…Thus, several other factors are playing a role to modulate incidence and severity of the disease. In humans, a correlation between HPA1a Ab titers in the mother and severity of the thrombocytopenia at birth has been reported, despite several analytical variation factors (35)(36)(37). FcRn, the neonatal IgG receptor, has been shown to modulate FNAIT in a mouse model (38).…”

Section: Discussionmentioning

confidence: 99%

Alloantibodies against MHC Class I: A Novel Mechanism of Neonatal Pancytopenia Linked to Vaccination

Foucras

Corbière

Tasca

et al. 2011

The Journal of Immunology

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Fetal/neonatal alloimmune thrombocytopenia is a frequent disease in humans where alloantibodies against platelet Ags lead to platelet destruction and hemorrhage. Although a role in the disease for Abs against MHC has been suspected, this has not been formally demonstrated. Since 2007, a hemorrhagic syndrome due to thrombocytopenia and designated as bovine neonatal pancytopenia (BNP) has been recognized in calves in several European countries. An inactivated antiviral vaccine is strongly suspected to be involved in this syndrome because of its highly frequent use in the dams of affected calves. In this study, we show that BNP is an alloimmune disease, as we reproduced the signs by transferring serum Abs from vaccinated BNP dams into healthy neonatal calves. Ab specificity was strongly associated with the presence of allogeneic MHC class I Abs in the dams. MHC class I staining was also observed on Madin–Darby bovine kidney cells, a cell line related to the one used to produce the vaccine Ag. Our report emphatically demonstrates that alloimmunization against MHC class I is associated with a substantial risk of developing cytopenia-associated syndromes in neonates when a cell line of the same species is used to produce an inactivated vaccine injected into the mother.

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Section: Discussionmentioning

confidence: 99%

Alloantibodies against MHC Class I: A Novel Mechanism of Neonatal Pancytopenia Linked to Vaccination

Foucras

Corbière

Tasca

et al. 2011

The Journal of Immunology

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“…Immunization against HPA-1a occurs in ;1:450 random pregnancies. [8][9][10] Although platelet decrement is related to antibody titer in FNAIT, 8,11,12 this correlation is not strict, as cases with low titers and very low platelet counts, as well as cases with high titers and normal platelet counts, are frequently observed. Recently we found that at least some of this discrepancy is due to differences in the functional quality of these antibodies, determined by its Fc glycosylation, in particular the level of core fucosylation.…”

Section: Introductionmentioning

confidence: 99%

C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

Kapur

Heitink‐Pollé

Porcelijn

et al. 2015

Blood

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Key Points• CRP enhances IgG-mediated respiratory burst and phagocytosis of platelets in vitro and their clearance in vivo.• CRP levels are increased in ITP patients and correlate with platelet counts and bleeding severity and predict time to recovery.Immune-mediated platelet destruction is most frequently caused by allo-or autoantibodies via Fcg receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein C-reactive protein (CRP), a ligand for Fc receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro and in vivo in mice. Without antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo-and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers, and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients. (Blood. 2015;125(11): 1793-1802 IntroductionFetal or neonatal alloimmune thrombocytopenia (FNAIT) and immune thrombocytopenia (ITP) are both antibody-mediated disorders in which platelets are destroyed mainly through activating immunoglobulin (IgG) Fc receptors on phagocytes in the spleen and liver, eventually resulting in thrombocytopenia. 1 In childhood, ITP is characterized by a typical history of acute development of purpura and bruising in an otherwise healthy child, caused by development of platelet autoantibodies, with an incidence of ;5 in 100 000 children.2 Most children with newly diagnosed ITP will not suffer from serious bleeding and will recover within 12 months. In ;60% of ITP, there is a history of a prior infection. [1][2][3] FNAIT is a potentially destructive disease in pregnancies, with intracerebral hemorrhage (ICH) of the fetus or neonate as the most feared complication, resulting in perinatal death in 1% to 7% or in severe neurological impairments in 14% to 26% of affected pregnancies. [4][5][6][7] FNAIT is caused by maternal IgG platelet alloantibodies, in whites mainly directed against human platelet antigen (HPA)-1a (85%), that cross the placenta and destroy the platelets of the fetus or newborn. Immunization against HPA-1a occurs in ;1:450 random pregnancies. [8][9][10] Although platelet decrement is related to antibody titer in FNAIT, 8,11,12 this correlation is not strict, as cas...

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“…Det kliniske forløpet ved føtal/neonatal alloimmun trombocytopeni er svaert varierende og spenner fra lett redusert trombocyttall med spontan normalisering til alvorlig trombocytopeni med intrakranial blød-ning og neonatal død. I flere studier er det vist sammenheng mellom antistoffnivået hos moren og trombocyttallet hos barnet (7,9). I tillegg er det vist at behandling av moren før fødselen med intravenøs injeksjon av polyklonalt immunglobulin og steroider reduserer forekomsten av hjerneblød-ninger (9,10).…”

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“…Kvinnen vil ha normalt trombocyttall og kan immuniseres i første svangerskap (25 %) eller i forbindelse med forløsningen (75 %). Dermed kan fosteret vaere affisert i første svangerskap (7). Dette står i kontrast til antistoffmediert hemolytisk sykdom hos nyfødte, der problemet sjelden oppstår i første svangerskap, men oftest i påfølgende uforlikelige svangerskap etter immunisering.…”

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Et nyfødt barn med petekkier

Eriksen¹,

Husebekk²,

Fugelseth³

et al. 2013

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A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Cited by 131 publications

References 26 publications

Alloantibodies against MHC Class I: A Novel Mechanism of Neonatal Pancytopenia Linked to Vaccination

Alloantibodies against MHC Class I: A Novel Mechanism of Neonatal Pancytopenia Linked to Vaccination

C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

Et nyfødt barn med petekkier

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