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.
Highlights
Bovine Neonatal Pancytopenia (BNP), a fatal bleeding syndrome in neonatal calves, is characterized by lymphocytopenia, thrombocytopenia, bone marrow hypoplasia and severe internal and external bleeding[1,2,3]
We showed that there was no association between the occurrence of BNP and Major Histocompatibility Complex class I (MHC I) haplotypes of dams or calves[12]
BNP is a fatal bleeding syndrome in neonatal calves caused by Pregsure© BVD vaccine-induced maternal alloantibodies absorbed from the colostrum
Summary
Bovine Neonatal Pancytopenia (BNP), a fatal bleeding syndrome in neonatal calves, is characterized by lymphocytopenia, thrombocytopenia, bone marrow hypoplasia and severe internal and external bleeding[1,2,3]. Epidemiological studies showed a strong association between the occurrence of BNP and vaccination of the mothers of affected calves with Pregsure© BVD (Pfizer Animal Health)[5]. It is likely that vaccination of dams with Pregsure© BVD induced alloantibodies which, upon ingestion of colostrum, elicited BNP in calves. We showed that there was no association between the occurrence of BNP and MHC I haplotypes of dams or calves[12]. MHC I is expressed on all nucleated cells, whereas BNP pathology is characterized by a loss of specific cell types (i.e. leukocytes, platelets and bone marrow cells)[1,2,3]. The goals of the present study were to i) assess the relative importance of anti-MHC I antibodies, ii) elucidate if BNP-associated alloantibodies recognize other targets, and iii) link the alloantibody specificity to the pathology of Bovine Neonatal Pancytopenia
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