Sera from dams of calves with bovine neonatal pancytopenia contain alloimmune antibodies directed against calf leukocytes

Pardon, Bart; Stuyven, Edith; Stuyvaert, Sabrina; Hostens, Miel; Dewulf, Jeroen; Goddeeris, Bruno; Cox, Eric; Deprez, Piet

doi:10.1016/j.vetimm.2011.02.017

Cited by 28 publications

(30 citation statements)

References 11 publications

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“…Indeed, BNP is clinically very similar to human neonatal thrombocytopenia and granulocytopenia with an alloimmune cause (8). Recent reports indicating that alloantibodies can be detected in the dams of affected calves support this hypothesis (9). However, Ab specificity and cause of BNP remained hidden until now.…”

Section: S Ince 2007 An Emergent Life-threatening Disease Of Neonatalmentioning

confidence: 96%

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: S Ince 2007 An Emergent Life-threatening Disease Of Neonatalmentioning

confidence: 96%

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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“…It presents as a bleeding disorder of calves less than one month old resulting in a high level of mortality in clinically affected calves [1,3] due to bone marrow trilineage hypoplasia [4] accompanied by depletion of peripheral thrombocytes and leukocytes. The disease is mediated by ingestion of alloantibodies in colostrum from particular cows [5,6] and the subsequent binding of these alloantibodies to calf hematopoietic cells [7,8], leading to functional compromise of bone marrow hematopoietic progenitors [9]. BNP is strongly associated with the use of a particular Bovine Viral Diarrhoea Virus (BVDV) vaccine (Pregsure BVD; Pfizer Animal Health) in the dams of affected calves [10,11] suggesting this vaccine induces alloantibody production in BNP dams.…”

Section: Introductionmentioning

confidence: 99%

Evidence of a high incidence of subclinically affected calves in a herd of cattle with fatal cases of Bovine Neonatal Pancytopenia (BNP)

Bell

Kerr²,

Scott

et al. 2014

BMC Vet Res

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BackgroundBovine Neonatal Pancytopenia (BNP) is a disease of calves characterised by bone marrow trilineage hypoplasia, mediated by ingestion of alloantibodies in colostrum. Suspected subclinical forms of BNP have been reported, suggesting that observed clinical cases may not represent the full extent of the disease. However to date there are no objective data available on the incidence of subclinical disease or its temporal distribution. This study aimed to 1) ascertain whether subclinical BNP occurs and, if so, to determine the incidence on an affected farm and 2) determine whether there is evidence of temporal clustering of BNP cases on this farm. To achieve these aims, haematological screening of calves born on the farm during one calving season was carried out, utilising blood samples collected at defined ages. These data were then analysed in comparison to data from both known BNP-free control animals and histopathologically confirmed BNP cases. An ordinal logistic regression model was used to create a composite haematology score to predict the probabilities of calves being normal, based on their haematology measurements at 10–14 days old.ResultsThis study revealed that 15% (21 of 139) of the clinically normal calves on this farm had profoundly abnormal haematology (<5% chance of being normal) and could be defined as affected by subclinical BNP. Together with clinical BNP cases, this gave the study farm a BNP incidence of 18%. Calves with BNP were found to be distributed throughout the calving period, with no clustering, and no significant differences in the date of birth of cases or subclinical cases were found compared to the rest of the calves. This study did not find any evidence of increased mortality or increased time from birth to sale in subclinical BNP calves but, as the study only involved a single farm and adverse effects may be determined by other inter-current diseases it remains possible that subclinical BNP has a detrimental impact on the health and productivity of calves under certain circumstances.ConclusionsSubclinical BNP was found to occur at a high incidence in a herd of cattle with fatal cases of BNP.

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“…Alloantibodies (also called isoantibodies) were found in colostrum and serum of BNP-dams with exhibited reactivity with leukocytes from susceptible calves [20-22]. According to our definition BNP-dams are animals, which have a common vaccination history with PregSure ® BVD and have given birth to at least one calf with confirmed BNP syndrome.…”

Section: Introductionmentioning

confidence: 99%

Vaccine-induced antibodies linked to bovine neonatal pancytopenia (BNP) recognize cattle major histocompatibility complex class I (MHC I)

Deutskens

Lamp

Riedel

et al. 2011

Vet Res

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A mysterious disease affecting calves, named bovine neonatal pancytopenia (BNP), emerged in 2007 in several European countries. Epidemiological studies revealed a connection between BNP and vaccination with an inactivated vaccine against bovine virus diarrhea (BVD). Alloantibodies reacting with blood leukocytes of calves were detected in serum and colostrum of dams, which have given birth to calves affected by BNP. To understand the linkage between vaccination and the development of alloantibodies, we determined the antigens reacting with these alloantibodies. Immunoprecipitation of surface proteins from bovine leukocytes and kidney cells using sera from dams with a confirmed case of BNP in their gestation history reacted with two dominant protein species of 44 and 12 kDa. These proteins were not detected by sera from dams, free of BVDV and not vaccinated against BVD, and from sera of animals vaccinated with a different inactivated BVD vaccine. The 44 kDa protein was identified by mass spectrometry analysis as MHC I, the other as β-2-microglobulin. The presence of major histocompatibility complex class I (MHC I) in the vaccine was confirmed by Western blot using a MHC I specific monoclonal antibody. A model of BNP pathogenesis is proposed.

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Sera from dams of calves with bovine neonatal pancytopenia contain alloimmune antibodies directed against calf leukocytes

Cited by 28 publications

References 11 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

Evidence of a high incidence of subclinically affected calves in a herd of cattle with fatal cases of Bovine Neonatal Pancytopenia (BNP)

Vaccine-induced antibodies linked to bovine neonatal pancytopenia (BNP) recognize cattle major histocompatibility complex class I (MHC I)

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