title: 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.
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.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. l.benedictus1@uu.nl.
authors.forename: Lindert
authors.initials: L
authors.lastname: Benedictus
authors.forename: Henny G
authors.initials: HG
authors.lastname: Otten
authors.forename: Gerdien
authors.initials: G
authors.lastname: van Schaik
authors.forename: Walter G J
authors.initials: WG
authors.lastname: van Ginkel
authors.forename: Henri C M
authors.initials: HC
authors.lastname: Heuven
authors.forename: Mirjam
authors.initials: M
authors.lastname: Nielen
authors.forename: Victor P M G
authors.initials: VP
authors.lastname: Rutten
authors.forename: Ad P
authors.initials: AP
authors.lastname: Koets
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000276:immunology; D003126:Colostrum / Q000276:immunology*; D005260:Female; D006239:Haplotypes; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D008285:Major Histocompatibility Complex; D010198:Pancytopenia / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D014611:Vaccination / Q000662:veterinary
chemical_list: D007518:Isoantibodies