title: Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class I expression.
abstract: 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.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Lindert
authors.initials: L
authors.lastname: Benedictus
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rutger D
authors.initials: RD
authors.lastname: Luteijn
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Henny
authors.initials: H
authors.lastname: Otten
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Robert Jan
authors.initials: RJ
authors.lastname: Lebbink
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Peter J S
authors.initials: PJ
authors.lastname: van Kooten
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Emmanuel J H J
authors.initials: EJ
authors.lastname: Wiertz
authors.affiliation: 1] Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands [2] Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa.
authors.forename: Victor P M G
authors.initials: VP
authors.lastname: Rutten
authors.affiliation: 1] Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands [2] Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ad P
authors.initials: AP
authors.lastname: Koets
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology*; D002460:Cell Line; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology*; D010198:Pancytopenia / Q000276:immunology / Q000662:veterinary*; D011247:Pregnancy; D014765:Viral Vaccines / Q000009:adverse effects*
chemical_list: D015395:Histocompatibility Antigens Class I; D019012:Integrin beta1; D007518:Isoantibodies; D014765:Viral Vaccines