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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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Binding of peripheral blood mononuclear cells by alloantibodies from Pregsure© BVD vaccinated dams.A: Peripheral Blood Mononuclear Cells (PBMC) from ten random dams were stained with serum (n = 3) and colostrum (n = 2) of different Pregsure© BVD vaccinated non-BNP dams (BNP-Vacc+, n = 5) and with serum (n = 3) and colostrum (n = 2) of Pregsure© BVD vaccinated BNP dams (BNP + Vacc+, n = 5). IgG1 alloantibody binding was measured by flow cytometry. GMFI subtracted by isotype control is plotted on the y-axis. The horizontal dotted line depicts the overall average geometric mean fluorescent intensity (GMFI) and the number above the plots describes the number of samples with a signal above the horizontal line. B: Correlation between the average IgG1 alloantibody binding of PBMC’s from ten dams to IgG1 alloantibody binding of MDBK cells by serum or colostrum samples as in Figure 3A. C: The data from Figure 3A were divided by the GMFI signal of the alloantibody staining of MDBK cells by the respective serum or colostrum. The horizontal dotted line depicts the overall average relative signal and the number above the plots describes the number of samples with a signal above the horizontal line. Mean ± standard error of the mean is depicted in all graphs. Two tailed simple T-tests for unequal variance was used to compare serum or colostrum alloantibody binding of PBMC’s between Pregsure© BVD vaccinated non-BNP and BNP dams. Correlation was tested with Pearsons correlation. Normality was tested with D’Agostino and Pearsons omnibus normality test.
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Fig3: Binding of peripheral blood mononuclear cells by alloantibodies from Pregsure© BVD vaccinated dams.A: Peripheral Blood Mononuclear Cells (PBMC) from ten random dams were stained with serum (n = 3) and colostrum (n = 2) of different Pregsure© BVD vaccinated non-BNP dams (BNP-Vacc+, n = 5) and with serum (n = 3) and colostrum (n = 2) of Pregsure© BVD vaccinated BNP dams (BNP + Vacc+, n = 5). IgG1 alloantibody binding was measured by flow cytometry. GMFI subtracted by isotype control is plotted on the y-axis. The horizontal dotted line depicts the overall average geometric mean fluorescent intensity (GMFI) and the number above the plots describes the number of samples with a signal above the horizontal line. B: Correlation between the average IgG1 alloantibody binding of PBMC’s from ten dams to IgG1 alloantibody binding of MDBK cells by serum or colostrum samples as in Figure 3A. C: The data from Figure 3A were divided by the GMFI signal of the alloantibody staining of MDBK cells by the respective serum or colostrum. The horizontal dotted line depicts the overall average relative signal and the number above the plots describes the number of samples with a signal above the horizontal line. Mean ± standard error of the mean is depicted in all graphs. Two tailed simple T-tests for unequal variance was used to compare serum or colostrum alloantibody binding of PBMC’s between Pregsure© BVD vaccinated non-BNP and BNP dams. Correlation was tested with Pearsons correlation. Normality was tested with D’Agostino and Pearsons omnibus normality test.

Mentions: Antibodies present in serum and colostrum from non-BNP and BNP dams bind PBMC (Figure 3A). Alloantibody binding of PBMC was significantly higher for both serum and colostrum of BNP dams compared to non-BNP dams. The number of PBMC samples that were positive were also higher for both serum and colostrum of BNP dams. However, average alloantibody binding of PBMC and alloantibody binding of MDBK cells had a high correlation (Figure 3B) and when alloantibody binding of PBMC was compensated for MDBK specific alloantibody levels to enable comparison of the binding of PBMC irrespective of total alloantibody levels, the relative signal was the same for BNP dams and non-BNP dams for serum as well as colostrum (Figure 3C). Also, the number of PBMC samples that were positive were similar in both groups for serum as well as colostrum. Results of individual serum and colostrum samples are shown in Additional file 7.Figure 3


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)

Binding of peripheral blood mononuclear cells by alloantibodies from Pregsure© BVD vaccinated dams.A: Peripheral Blood Mononuclear Cells (PBMC) from ten random dams were stained with serum (n = 3) and colostrum (n = 2) of different Pregsure© BVD vaccinated non-BNP dams (BNP-Vacc+, n = 5) and with serum (n = 3) and colostrum (n = 2) of Pregsure© BVD vaccinated BNP dams (BNP + Vacc+, n = 5). IgG1 alloantibody binding was measured by flow cytometry. GMFI subtracted by isotype control is plotted on the y-axis. The horizontal dotted line depicts the overall average geometric mean fluorescent intensity (GMFI) and the number above the plots describes the number of samples with a signal above the horizontal line. B: Correlation between the average IgG1 alloantibody binding of PBMC’s from ten dams to IgG1 alloantibody binding of MDBK cells by serum or colostrum samples as in Figure 3A. C: The data from Figure 3A were divided by the GMFI signal of the alloantibody staining of MDBK cells by the respective serum or colostrum. The horizontal dotted line depicts the overall average relative signal and the number above the plots describes the number of samples with a signal above the horizontal line. Mean ± standard error of the mean is depicted in all graphs. Two tailed simple T-tests for unequal variance was used to compare serum or colostrum alloantibody binding of PBMC’s between Pregsure© BVD vaccinated non-BNP and BNP dams. Correlation was tested with Pearsons correlation. Normality was tested with D’Agostino and Pearsons omnibus normality test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Binding of peripheral blood mononuclear cells by alloantibodies from Pregsure© BVD vaccinated dams.A: Peripheral Blood Mononuclear Cells (PBMC) from ten random dams were stained with serum (n = 3) and colostrum (n = 2) of different Pregsure© BVD vaccinated non-BNP dams (BNP-Vacc+, n = 5) and with serum (n = 3) and colostrum (n = 2) of Pregsure© BVD vaccinated BNP dams (BNP + Vacc+, n = 5). IgG1 alloantibody binding was measured by flow cytometry. GMFI subtracted by isotype control is plotted on the y-axis. The horizontal dotted line depicts the overall average geometric mean fluorescent intensity (GMFI) and the number above the plots describes the number of samples with a signal above the horizontal line. B: Correlation between the average IgG1 alloantibody binding of PBMC’s from ten dams to IgG1 alloantibody binding of MDBK cells by serum or colostrum samples as in Figure 3A. C: The data from Figure 3A were divided by the GMFI signal of the alloantibody staining of MDBK cells by the respective serum or colostrum. The horizontal dotted line depicts the overall average relative signal and the number above the plots describes the number of samples with a signal above the horizontal line. Mean ± standard error of the mean is depicted in all graphs. Two tailed simple T-tests for unequal variance was used to compare serum or colostrum alloantibody binding of PBMC’s between Pregsure© BVD vaccinated non-BNP and BNP dams. Correlation was tested with Pearsons correlation. Normality was tested with D’Agostino and Pearsons omnibus normality test.
Mentions: Antibodies present in serum and colostrum from non-BNP and BNP dams bind PBMC (Figure 3A). Alloantibody binding of PBMC was significantly higher for both serum and colostrum of BNP dams compared to non-BNP dams. The number of PBMC samples that were positive were also higher for both serum and colostrum of BNP dams. However, average alloantibody binding of PBMC and alloantibody binding of MDBK cells had a high correlation (Figure 3B) and when alloantibody binding of PBMC was compensated for MDBK specific alloantibody levels to enable comparison of the binding of PBMC irrespective of total alloantibody levels, the relative signal was the same for BNP dams and non-BNP dams for serum as well as colostrum (Figure 3C). Also, the number of PBMC samples that were positive were similar in both groups for serum as well as colostrum. Results of individual serum and colostrum samples are shown in Additional file 7.Figure 3

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