Abstract
BackgroundBovine neonatal pancytopenia (BNP) is a syndrome characterised by thrombocytopenia associated with marked bone marrow destruction in calves, widely reported since 2007 in several European countries and since 2011 in New Zealand. The disease is epidemiologically associated with the use of an inactivated bovine virus diarrhoea (BVD) vaccine and is currently considered to be caused by absorption of colostral antibody produced by some vaccinated cows (“BNP dams”). Alloantibodies capable of binding to the leukocyte surface have been detected in BNP dams and antibodies recognising bovine MHC class I and β-2-microglobulin have been detected in vaccinated cattle. In this study, calves were challenged with pooled colostrum collected from BNP dams or from non-BNP dams and their bone marrow hematopoietic progenitor cells (HPC) cultured in vitro from sternal biopsies taken at 24 hours and 6 days post-challenge.ResultsClonogenic assay demonstrated that CFU-GEMM (colony forming unit-granulocyte/erythroid/macrophage/megakaryocyte; pluripotential progenitor cell) colony development was compromised from HPCs harvested as early as 24 hour post-challenge. By 6 days post challenge, HPCs harvested from challenged calves failed to develop CFU-E (erythroid) colonies and the development of both CFU-GEMM and CFU-GM (granulocyte/macrophage) was markedly reduced.ConclusionThis study suggests that the bone marrow pathology and clinical signs associated with BNP are related to an insult which compromises the pluripotential progenitor cell within the first 24 hours of life but that this does not initially include all cell types.
Highlights
Bovine neonatal pancytopenia (BNP) is a syndrome characterised by thrombocytopenia associated with marked bone marrow destruction in calves, widely reported since 2007 in several European countries and since 2011 in New Zealand
While the identity of the target antigen(s) is unconfirmed, evidence supporting the presence of antibovine MHC Class I antibodies in BNP dams [14] and induction of anti-bovine MHC Class I antibodies by the implicated vaccine has recently been described [15]
We describe here a pilot study on the utility of bone marrow hematopoietic progenitor cell (BM-hematopoietic progenitor cells (HPC)) cultures to assess the functional compromise of harvested bovine BM-HPCs at 24 hours and 6 days post challenge with either pooled BNP dam colostrum or pooled normal colostrum
Summary
Bovine neonatal pancytopenia (BNP) is a syndrome characterised by thrombocytopenia associated with marked bone marrow destruction in calves, widely reported since 2007 in several European countries and since 2011 in New Zealand. Antibodies present in serum of BNP dams have been shown to be capable of binding to peripheral leukocytes and to cells in bone marrow smears of unrelated normal calves [12] and were detected bound to leukocytes of affected calves [9,13]. Such studies support the hypothesis that maternally derived colostral alloantibody targeting a bovine antigen (or antigens) causes the bone marrow pathology in calves. While the identity of the target antigen(s) is unconfirmed, evidence supporting the presence of antibovine MHC Class I antibodies in BNP dams [14] and induction of anti-bovine MHC Class I antibodies by the implicated vaccine has recently been described [15]
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