Alloantibodies against MHC Class I: A Novel Mechanism of Neonatal Pancytopenia Linked to Vaccination

Alloantibodies against MHC Class I: A Novel Mechanism of Neonatal Pancytopenia Linked to Vaccination
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DOI:
10.4049/jimmunol.1102533
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发表时间:
2011-12-15
影响因子:
4.4
通讯作者:
Schelcher, Francois
Schelcher, Francois
中科院分区:
医学2区
文献类型:
--
作者:
Foucras, Gilles;Corbiere, Fabien;Schelcher, Francois

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胎儿/新生儿同种免疫性血小板减少症是人类常见的疾病,其中针对血小板Ag的同种抗体导致血小板破坏和出血。虽然抗MHC抗体在疾病中的作用已被怀疑,但这尚未得到正式证实。自2007年以来,在几个欧洲国家的小牛中发现了由血小板减少症引起的出血性综合征,称为牛新生儿全血细胞减少症(BNP)。一种灭活的抗病毒疫苗被强烈怀疑与这种综合征有关,因为它在受影响小牛的母体中使用频率很高。在这项研究中,我们表明,BNP是一种同种免疫性疾病,因为我们通过将血清抗体从接种BNP的母畜转移到健康的新生小牛中来重现这些体征。抗体特异性与母体中同种异体MHC I类抗体的存在密切相关。在Madin-Darby牛肾细胞(与用于生产疫苗Ag的细胞系相关的细胞系)上也观察到MHC I类染色。我们的报告强调表明,同种免疫对MHC I类是与一个实质性的风险发展中的血细胞减少相关综合征的新生儿时,同一物种的细胞系用于生产灭活疫苗注射到母亲。免疫学杂志,2011,187:6564-6570。
Fetal/neonatal alloimmune thrombocytopenia is a frequent disease in humans where alloantibodies against platelet Ags lead to platelet destruction and hemorrhage. Although a role in the disease for Abs against MHC has been suspected, this has not been formally demonstrated. Since 2007, a hemorrhagic syndrome due to thrombocytopenia and designated as bovine neonatal pancytopenia (BNP) has been recognized in calves in several European countries. An inactivated antiviral vaccine is strongly suspected to be involved in this syndrome because of its highly frequent use in the dams of affected calves. In this study, we show that BNP is an alloimmune disease, as we reproduced the signs by transferring serum Abs from vaccinated BNP dams into healthy neonatal calves. Ab specificity was strongly associated with the presence of allogeneic MHC class I Abs in the dams. MHC class I staining was also observed on Madin-Darby bovine kidney cells, a cell line related to the one used to produce the vaccine Ag. Our report emphatically demonstrates that alloimmunization against MHC class I is associated with a substantial risk of developing cytopenia-associated syndromes in neonates when a cell line of the same species is used to produce an inactivated vaccine injected into the mother. The Journal of Immunology, 2011, 187: 6564-6570.