Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class 1 expression

L. Benedictus, Rutger D. Luteijn, H. Otten, Robert Jan Lebbink, P.J.S. van Kooten, E.J.H.J. Wiertz, Victor P.M.G. Rutten, A.P. Koets

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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.
Original languageEnglish
Article number12748
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015

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Isoantibodies
Pancytopenia
Major Histocompatibility Complex
Virulence
Vaccines
Integrins
Mothers
Viral Vaccines
Lymphopenia
Inactivated Vaccines
Colostrum
Isoantigens
Third Pregnancy Trimester
Thrombocytopenia
Fetus
Bone Marrow

Cite this

Benedictus, L. ; Luteijn, Rutger D. ; Otten, H. ; Lebbink, Robert Jan ; van Kooten, P.J.S. ; Wiertz, E.J.H.J. ; Rutten, Victor P.M.G. ; Koets, A.P. / Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class 1 expression. In: Scientific Reports. 2015 ; Vol. 5.
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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.",
author = "L. Benedictus and Luteijn, {Rutger D.} and H. Otten and Lebbink, {Robert Jan} and {van Kooten}, P.J.S. and E.J.H.J. Wiertz and Rutten, {Victor P.M.G.} and A.P. Koets",
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Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class 1 expression. / Benedictus, L.; Luteijn, Rutger D.; Otten, H.; Lebbink, Robert Jan; van Kooten, P.J.S.; Wiertz, E.J.H.J.; Rutten, Victor P.M.G.; Koets, A.P.

In: Scientific Reports, Vol. 5, 12748, 2015.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Benedictus, L.

AU - Luteijn, Rutger D.

AU - Otten, H.

AU - Lebbink, Robert Jan

AU - van Kooten, P.J.S.

AU - Wiertz, E.J.H.J.

AU - Rutten, Victor P.M.G.

AU - Koets, A.P.

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AB - 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.

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