Benedictus Lindert, Otten Henny G, van Schaik Gerdien, van Ginkel Walter G J, Heuven Henri C M, Nielen Mirjam, Rutten Victor P M G, Koets Ad P
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Vet Res. 2014 Dec 17;45(1):129. doi: 10.1186/s13567-014-0129-0.
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.
牛新生儿全血细胞减少症(BNP)是新生犊牛的一种出血综合征,由特定母牛初乳中吸收的同种抗体引起。一种商业性牛病毒性腹泻疫苗可能是引发与BNP相关同种抗体的同种抗原来源。我们推测,接种疫苗的母牛所生犊牛中BNP的罕见发生可能与母牛和犊牛的基因差异有关。我们发现,犊牛体内BNP的发生是母牛的一种可遗传性状,而非犊牛的,且遗传力较高,为19%。为了阐明哪些基因在BNP的发生中起作用,我们对候选基因进行了测序,并对BNP同种抗体进行了表征。疫苗中存在的同种抗原必须通过MHC II类分子呈递给母牛的免疫系统,然而DRB3测序显示,BNP母牛和非BNP母牛之间的MHC II类单倍型没有差异。MHC I类分子是一种高度多态的同种抗原,是BNP同种抗体的重要靶点。使用一种基于新序列的MHC I类分型方法,我们发现BNP与母牛或犊牛的MHC I类单倍型分布没有关联。在接种疫苗的BNP母牛和非BNP母牛中均检测到同种抗体,且我们发现这两组之间的同种抗体特征没有差异,但BNP母牛中的同种抗体水平显著更高。我们得出结论,犊牛中BNP的发生是母牛而非犊牛的可遗传性状,BNP母牛和非BNP母牛之间的基因差异可能是由于控制接种疫苗后定量同种抗体反应的基因所致。