Bovine Neonatal Pancytopenia-Associated Alloantibodies Recognize Individual Bovine Leukocyte Antigen 1 Alleles.

Bovine Neonatal Pancytopenia-Associated Alloantibodies Recognize Individual Bovine Leukocyte Antigen 1 Alleles.
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DOI:
10.3389/fimmu.2018.01902
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发表时间:
2018
影响因子:
7.3
通讯作者:
Bastian M
Bastian M
中科院分区:
医学2区
文献类型:
--
作者:
Kasonta R;Mauritz J;Spohr C;Sauter-Louis C;Duchow K;Cussler K;Holsteg M;Bastian M

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牛新生儿全血细胞减少症(BNP)是一种在幼龄犊牛中观察到的疫苗诱导的同种免疫疾病,其特征是血液循环、全血细胞减少和造血组织严重破坏。BNP是由同种异体反应性母源抗体诱导的,这些母源抗体存在于接种高佐剂牛病毒性腹泻疫苗的某些奶牛的初乳中。源自疫苗生产细胞系的生物工艺杂质可能诱导了这些同种异体反应性抗体。一种由疫苗诱导的同种异体抗体识别的突出同种异体抗原是高度多态的牛主要组织相容性复合物I类抗原(牛白细胞抗原1-BoLA I)。本研究的目的是确定BNP相关的抗BoLA I同种抗体的精细特异性。总共鉴定了来自生产细胞系的8种不同BoLA I等位基因。克隆所有基因并在鼠细胞系中重组表达。在流式细胞术测定中使用这些细胞,证明BNP母体血清中存在BoLA I特异性同种抗体。鉴定了三种BoLA I变体,其占疫苗诱导的BoLA I反应性的大部分。通过比较免疫原性与非免疫原性BoLA I变体的序列,鉴定了BoLA I上可能的最小表位。一般而言,BNP小牛的母体显示出高水平的BoLA I反应性同种抗体,而接种疫苗的母牛分娩健康小牛的同种抗体滴度显著较低。我们确定了一个接种母牛亚组,其中健康小牛显示出非常高的同种抗体滴度。在这些奶牛和BNP母体之间,未观察到BoLA I反应性模式的主要差异。然而,通过一组有限的母畜-小牛对,可以证明这些奶牛的血清不与其后代的表达BoLA I的白细胞结合。相比之下,当用相应母畜血清测试存活BNP小牛的细胞时,存在显着结合。因此,我们得出结论,主要是高同种异体反应的奶牛有风险诱导BNP,它取决于父系遗传的BoLA I小牛是否开发BNP。
Bovine neonatal pancytopenia (BNP) was a vaccine-induced alloimmune disease observed in young calves and characterized by hemorrhages, pancytopenia, and severe destruction of the hematopoietic tissues. BNP was induced by alloreactive maternal antibodies present in the colostrum of certain cows vaccinated with a highly adjuvanted vaccine against bovine viral diarrhea. Bioprocess impurities, originating from the production cell line of the vaccine, are likely to have induced these alloreactive antibodies. One prominent alloantigen recognized by vaccine-induced alloantibodies is highly polymorphic bovine major histocompatibility complex class I antigen (bovine leukocyte antigen 1—BoLA I). Aim of this study was to define the fine specificity of BNP-associated anti-BoLA I alloantibodies. In total, eight different BoLA I alleles from the production cell line were identified. All genes were cloned and recombinantly expressed in murine cell lines. Using these cells in a flow cytometric assay, the presence of BoLA I specific alloantibodies in BNP dam sera was proven. Three BoLA I variants were identified that accounted for the majority of vaccine-induced BoLA I reactivity. By comparing the sequence of immunogenic to non-immunogenic BoLA I variants probable minimal epitopes on BoLA I were identified. In general, dams of BNP calves displayed high levels of BoLA I reactive alloantibodies, while vaccinated cows delivering healthy calves had significantly lower alloantibody titers. We identified a subgroup of vaccinated cows with healthy calves displaying very high alloantibody titers. Between these cows and BNP dams no principle difference in the BoLA I reactivity pattern was observed. However, with a limited set of dam-calf pairs it could be demonstrated that serum from these cows did not bind to BoLA I expressing leukocytes of their offspring. By contrast, when testing cells from surviving BNP calves with the corresponding dam’s serum there was significant binding. We therefore conclude that predominantly highly alloreactive cows are at risk to induce BNP and it depends on the paternally inherited BoLA I whether or not the calf develops BNP.
DOI: 10.1371/journal.pone.0034183
发表时间: 2012-05-11
期刊: PLOS ONE
影响因子: 3.7
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期刊: ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 2
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发表时间: 2011-12-15
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发表时间: 2012-10-19
期刊: VACCINE
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