Lack of evidence for an association between MHC diversity and the development of bovine neonatal pancytopenia in Holstein dairy cattle

Ballingall, Keith T.; Nath, Mintu; Holliman, Andrew; Laming, Eleanor; Steele, Philip; Willoughby, Kim

doi:10.1016/j.vetimm.2011.01.017

Cited by 9 publications

(8 citation statements)

References 14 publications

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“…To ensure that the calves represented a broad range of MHC genotypes, each calf was genotyped at the highly polymorphic MHC class II DRB3 [16]. The MHC genotypes of each calf were as follows; W, DRB3*1001, DRB3*1201 ; X, DRB3*1001, DRB3*1501; Y, DRB3*0101, DRB3*1001 and Z, DRB3*1201, DRB3*1201.…”

Section: Methodsmentioning

confidence: 99%

“…While no linkage to MHC-class II nor factor XI has been detected in affected calves there is some evidence that within herds, specific groups or lines of animals may be more frequently affected, suggesting that some cows are more at risk of BNP-associated alloantibody production due to either intrinsic factors or to interaction between the pregnant cow and its fetus [16,17]. …”

Section: Introductionmentioning

confidence: 99%

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Demonstration of early functional compromise of bone marrow derived hematopoietic progenitor cells during bovine neonatal pancytopenia through in vitro culture of bone marrow biopsies

et al. 2012

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BackgroundBovine neonatal pancytopenia (BNP) is a syndrome characterised by thrombocytopenia associated with marked bone marrow destruction in calves, widely reported since 2007 in several European countries and since 2011 in New Zealand. The disease is epidemiologically associated with the use of an inactivated bovine virus diarrhoea (BVD) vaccine and is currently considered to be caused by absorption of colostral antibody produced by some vaccinated cows (“BNP dams”). Alloantibodies capable of binding to the leukocyte surface have been detected in BNP dams and antibodies recognising bovine MHC class I and β-2-microglobulin have been detected in vaccinated cattle. In this study, calves were challenged with pooled colostrum collected from BNP dams or from non-BNP dams and their bone marrow hematopoietic progenitor cells (HPC) cultured in vitro from sternal biopsies taken at 24 hours and 6 days post-challenge.ResultsClonogenic assay demonstrated that CFU-GEMM (colony forming unit-granulocyte/erythroid/macrophage/megakaryocyte; pluripotential progenitor cell) colony development was compromised from HPCs harvested as early as 24 hour post-challenge. By 6 days post challenge, HPCs harvested from challenged calves failed to develop CFU-E (erythroid) colonies and the development of both CFU-GEMM and CFU-GM (granulocyte/macrophage) was markedly reduced.ConclusionThis study suggests that the bone marrow pathology and clinical signs associated with BNP are related to an insult which compromises the pluripotential progenitor cell within the first 24 hours of life but that this does not initially include all cell types.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Demonstration of early functional compromise of bone marrow derived hematopoietic progenitor cells during bovine neonatal pancytopenia through in vitro culture of bone marrow biopsies

et al. 2012

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“…A genetic etiology of BNP was discussed, but BNP appearance showed no link to certain genotypes. Epidemiological studies showed that mutations in coagulation factor XI [11] or certain MHC class II haplotypes [12] were not associated with BNP outbreaks. In BNP affected calves, the often dramatic decline of thrombocyte and leukocyte counts within the first hours after ingestion of colostrum, together with the characteristic bone marrow findings (panmyelophthisis, phagocytic bone marrow macrophages) led to the assumption of an immune mediated process [13,14].…”

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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“…This is consistent with the nature of MHC I sequence polymorphism, where short stretches of amino acids are frequently shared by different alleles. Consequently, BNP cows and calves are both likely to have a wide range of different MHC I genotypes, which explains why no association has been found between specific MHC haplotypes and the occurrence of BNP [34,35] and why BNP is not a heritable trait for calves [35].…”

confidence: 99%

The risks of using allogeneic cell lines for vaccine production: the example of Bovine Neonatal Pancytopenia

Benedictus

Bell

2016

Expert Review of Vaccines

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Introduction: Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for major-histocompatibility class I antigens are transferred from the mother to the calf via colostrum, leading to profound depletion of peripheral blood and bone marrow cells that is often fatal. Areas covered: Pubmed and Web of Science were used to search for literature relevant to BNP and the use of allogeneic vaccine cell lines. Following a review of the pathology and pathogenesis of this novel condition, we discuss potential risks associated with the use of allogeneic vaccine cell lines. Expert commentary: Although BNP is associated with a specific vaccine, it highlights safety concerns common to all vaccines produced using allogeneic cell lines. Measures to prevent similar vaccineinduced alloimmune-mediated adverse events in the future are discussed.

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Lack of evidence for an association between MHC diversity and the development of bovine neonatal pancytopenia in Holstein dairy cattle

Cited by 9 publications

References 14 publications

Demonstration of early functional compromise of bone marrow derived hematopoietic progenitor cells during bovine neonatal pancytopenia through in vitro culture of bone marrow biopsies

Demonstration of early functional compromise of bone marrow derived hematopoietic progenitor cells during bovine neonatal pancytopenia through in vitro culture of bone marrow biopsies

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

The risks of using allogeneic cell lines for vaccine production: the example of Bovine Neonatal Pancytopenia

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