Bovine neonatal pancytopenia (BNP): novel insights into the incidence, vaccination-associated epidemiological factors and a potential genetic predisposition for clinical and subclinical cases

Demasius, Wiebke; Weikard, Rosemarie; Kromik, Andreas; Wolf, Carola; Müller, Kerstin; Kühn, Christa

doi:10.1016/j.rvsc.2014.03.019

Cited by 9 publications

(7 citation statements)

References 27 publications

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“…Genetic variation in the paternal haplotype of the calves is not related to the development of BNP in the calf, since the heritability of the development of BNP in calves born to Pregsure© BVD vaccinated dams is 0%. Demasius et al [ 21 ] found that in an experimental German Holstein x Charolois crossbred herd with a limited number of sire lines, all BNP cases were restricted to a single maternal grandsire, also indicating the importance of the genetic background of the dam. In addition from a limited number of BNP dams was shown to induce BNP in randomly selected healthy calves [ 8 - 10 ] which supports the notion that the genetic background of the calf is not critical.…”

Section: Discussionmentioning

confidence: 99%

Bovine Neonatal Pancytopenia is a heritable trait of the dam rather than the calf and correlates with the magnitude of vaccine induced maternal alloantibodies not the MHC haplotype

Benedictus

Otten

Schaik

et al. 2014

Vet Res

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Bovine Neonatal Pancytopenia (BNP), a bleeding syndrome of neonatal calves, is caused by alloantibodies absorbed from the colostrum of particular cows. A commercial BVD vaccine is the likely source of alloantigens eliciting BNP associated alloantibodies. We hypothesized that the rare occurrence of BNP in calves born to vaccinated dams could be associated with genetic differences within dams and calves. We found that the development of BNP within calves was a heritable trait for dams, not for calves and had a high heritability of 19%. To elucidate which genes play a role in the development of BNP we sequenced candidate genes and characterized BNP alloantibodies. Alloantigens present in the vaccine have to be presented to the dam’s immune system via MHC class II, however sequencing of DRB3 showed no differences in MHC class II haplotype between BNP and non-BNP dams. MHC class I, a highly polymorphic alloantigen, is an important target of BNP alloantibodies. Using a novel sequence based MHC class I typing method, we found no association of BNP with MHC class I haplotype distribution in dams or calves. Alloantibodies were detected in both vaccinated BNP and non-BNP dams and we found no differences in alloantibody characteristics between these groups, but alloantibody levels were significantly higher in BNP dams. We concluded that the development of BNP in calves is a heritable trait of the dam rather than the calf and genetic differences between BNP and non-BNP dams are likely due to genes controlling the quantitative alloantibody response following vaccination.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-014-0129-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Bovine Neonatal Pancytopenia is a heritable trait of the dam rather than the calf and correlates with the magnitude of vaccine induced maternal alloantibodies not the MHC haplotype

Benedictus

Otten

Schaik

et al. 2014

Vet Res

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“…leukocytes, platelets and bone marrow cells) 1 2 3 . Some authors have therefore argued that alloantibodies with a different specificity than MHC I might better explain the pathogenesis of BNP 7 13 14 . The goals of the present study were to i) assess the relative importance of anti-MHC I antibodies, ii) elucidate if BNP-associated alloantibodies recognize other targets, and iii) link the alloantibody specificity to the pathology of Bovine Neonatal Pancytopenia.…”

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confidence: 99%

Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class I expression

Benedictus

Luteijn

Otten

et al. 2015

Sci Rep

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Bovine Neonatal Pancytopenia (BNP), a fatal bleeding syndrome of neonatal calves, is caused by maternal alloantibodies absorbed from colostrum and is characterized by lymphocytopenia, thrombocytopenia and bone marrow hypoplasia. An inactivated viral vaccine is the likely source of alloantigens inducing BNP-associated alloantibodies in the dam. In this study the specificity of BNP alloantibodies was assessed and was linked to the pathology of BNP. We demonstrated that Major Histocompatibility Complex class I (MHC I) and Very Late Antigen-3, an integrin α3/β1 heterodimer, were the major targets of BNP alloantibodies. However, alloantibody binding to various bovine cell types correlated with MHC I expression, rather than integrin β1 or α3 expression. Likewise, alloantibody-dependent complement-mediated cell lysis correlated strongly with MHC I expression. Examination of several tissues of third trimester bovine foetuses revealed that cells, shown to be affected in calves with BNP, were characterized by high MHC class I expression and high levels of alloantibody binding. We conclude that in spite of the heterogeneous specificity of BNP associated maternal alloantibodies, MHC I-specific antibodies mediate the pathogenicity of BNP in the calf and that cells with high MHC I expression were preferentially affected in BNP.

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“…This group also hypothesized, that differences between BNP and control dams are likely due to genes controlling the quantitative alloantibody response after vaccination (22). To find evidence for a genetic predisposition of this immune deviant BNP phenotype in cows (22, 23), we additionally analyzed the immune phenotypes of 121 non-PregSure BVD vaccinated cows. In our study, 22% of cows (ID cows) showed a BNP-like hyperproliferative response to T cell stimulation in vitro (ID, Figures 6A,B).…”

Section: Discussionmentioning

confidence: 99%

A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence

K¹,

Kleinwort²,

Hobmaier³

et al. 2018

Front. Immunol.

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A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5–10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.

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Bovine neonatal pancytopenia (BNP): novel insights into the incidence, vaccination-associated epidemiological factors and a potential genetic predisposition for clinical and subclinical cases

Cited by 9 publications

References 27 publications

Bovine Neonatal Pancytopenia is a heritable trait of the dam rather than the calf and correlates with the magnitude of vaccine induced maternal alloantibodies not the MHC haplotype

Bovine Neonatal Pancytopenia is a heritable trait of the dam rather than the calf and correlates with the magnitude of vaccine induced maternal alloantibodies not the MHC haplotype

Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class I expression

A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence

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