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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 L, Otten HG, van Schaik G, van Ginkel WG, Heuven HC, Nielen M, Rutten VP, Koets AP - Vet. Res. (2014)

Bottom Line: 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%.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. l.benedictus1@uu.nl.

ABSTRACT
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.

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Isotype characterization of alloantibodies from Pregsure© BVD vaccinated dams. Flow cytrometry was used to measure the isotype of alloantibodies binding to MDBK cells in serum (Ser) or colostrum (Col) from i) dams not vaccinated with Pregsure© BVD (BNP-VAcc-) ii) Pregsure© BVD vaccinated non-BNP dams (BNP-Vacc+) and iii) Pregsure© BVD vaccinated BNP dams (BNP + Vacc+). All results were compared by two tailed simple T-tests for unequal variance. Within each isotype, all groups are compared to the non Pregsure© BVD vaccinated dams (Ser BNP-Vacc-). To adjust for multiple comparison, the False Discovery Rate (FDR) was controlled at 5% using the principle from Benjamini and Hochberg [19]. The largest P-value lower than its FDR-derived significance threshold and all P-values smaller are significant and are depicted by an asterisk (*). GMFI = Geometric Mean Fluorescent Intensity.
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Fig2: Isotype characterization of alloantibodies from Pregsure© BVD vaccinated dams. Flow cytrometry was used to measure the isotype of alloantibodies binding to MDBK cells in serum (Ser) or colostrum (Col) from i) dams not vaccinated with Pregsure© BVD (BNP-VAcc-) ii) Pregsure© BVD vaccinated non-BNP dams (BNP-Vacc+) and iii) Pregsure© BVD vaccinated BNP dams (BNP + Vacc+). All results were compared by two tailed simple T-tests for unequal variance. Within each isotype, all groups are compared to the non Pregsure© BVD vaccinated dams (Ser BNP-Vacc-). To adjust for multiple comparison, the False Discovery Rate (FDR) was controlled at 5% using the principle from Benjamini and Hochberg [19]. The largest P-value lower than its FDR-derived significance threshold and all P-values smaller are significant and are depicted by an asterisk (*). GMFI = Geometric Mean Fluorescent Intensity.

Mentions: Isotype specific alloantibody binding of MDBK cells is shown in Figure 2. IgG1 alloantibodies were most abundant and the levels were significantly higher in serum of non-BNP dams and in serum and colostrum of BNP dams compared to dams not vaccinated with Pregsure© BVD. IgG2 alloantibody levels were significantly higher in serum and colostrum of BNP dams compared to dams not vaccinated with Pregsure© BVD. IgG2 alloantibody levels tended to be higher in non-BNP dams as well, but due to higher variation among dams, did not differ significantly from that in dams not vaccinated with Pregsure© BVD. For IgM and IgA there were no significant differences between groups.Figure 2


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 L, Otten HG, van Schaik G, van Ginkel WG, Heuven HC, Nielen M, Rutten VP, Koets AP - Vet. Res. (2014)

Isotype characterization of alloantibodies from Pregsure© BVD vaccinated dams. Flow cytrometry was used to measure the isotype of alloantibodies binding to MDBK cells in serum (Ser) or colostrum (Col) from i) dams not vaccinated with Pregsure© BVD (BNP-VAcc-) ii) Pregsure© BVD vaccinated non-BNP dams (BNP-Vacc+) and iii) Pregsure© BVD vaccinated BNP dams (BNP + Vacc+). All results were compared by two tailed simple T-tests for unequal variance. Within each isotype, all groups are compared to the non Pregsure© BVD vaccinated dams (Ser BNP-Vacc-). To adjust for multiple comparison, the False Discovery Rate (FDR) was controlled at 5% using the principle from Benjamini and Hochberg [19]. The largest P-value lower than its FDR-derived significance threshold and all P-values smaller are significant and are depicted by an asterisk (*). GMFI = Geometric Mean Fluorescent Intensity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4269077&req=5

Fig2: Isotype characterization of alloantibodies from Pregsure© BVD vaccinated dams. Flow cytrometry was used to measure the isotype of alloantibodies binding to MDBK cells in serum (Ser) or colostrum (Col) from i) dams not vaccinated with Pregsure© BVD (BNP-VAcc-) ii) Pregsure© BVD vaccinated non-BNP dams (BNP-Vacc+) and iii) Pregsure© BVD vaccinated BNP dams (BNP + Vacc+). All results were compared by two tailed simple T-tests for unequal variance. Within each isotype, all groups are compared to the non Pregsure© BVD vaccinated dams (Ser BNP-Vacc-). To adjust for multiple comparison, the False Discovery Rate (FDR) was controlled at 5% using the principle from Benjamini and Hochberg [19]. The largest P-value lower than its FDR-derived significance threshold and all P-values smaller are significant and are depicted by an asterisk (*). GMFI = Geometric Mean Fluorescent Intensity.
Mentions: Isotype specific alloantibody binding of MDBK cells is shown in Figure 2. IgG1 alloantibodies were most abundant and the levels were significantly higher in serum of non-BNP dams and in serum and colostrum of BNP dams compared to dams not vaccinated with Pregsure© BVD. IgG2 alloantibody levels were significantly higher in serum and colostrum of BNP dams compared to dams not vaccinated with Pregsure© BVD. IgG2 alloantibody levels tended to be higher in non-BNP dams as well, but due to higher variation among dams, did not differ significantly from that in dams not vaccinated with Pregsure© BVD. For IgM and IgA there were no significant differences between groups.Figure 2

Bottom Line: 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%.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. l.benedictus1@uu.nl.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus