Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Munich, Germany.
Research Unit for Protein Science, Helmholtz Zentrum Munich, German Research Center for Environmental Health GmbH, Munich, Germany.
Front Immunol. 2018 Dec 6;9:2884. doi: 10.3389/fimmu.2018.02884. eCollection 2018.
A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5-10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.
一种新型牛病毒性腹泻(BVD)疫苗可导致 5-10%的 BVD 疫苗接种牛产生致病性抗体。这些抗体通过初乳转移可导致牛新生全血细胞减少症(BNP),致死率为 90%。目前,对于 BNP 发病的确切免疫学机制尚不完全清楚。为了进一步深入了解这些机制,我们分析了同种反应性抗体产生者(BNP 牛)和非反应者的免疫蛋白质组。在刺激外周血衍生淋巴细胞(PBL)后,我们在 BNP 细胞中检测到几个免疫反应主要调节剂的表达水平明显异常,表明 BNP 牛的免疫表型发生改变,免疫反应严重失调。有趣的是,我们还在 22%的非 BVD 疫苗接种牛中发现了这种反应模式,表明这种免疫异常(ID)表型在牛中存在遗传倾向。我们还在 38 个月的回顾性研究中分析了 ID 表型与 10 个健康参数和 6 种疾病的功能相关性。ID 牛中乳腺炎的显著高发率强调了这种异常免疫反应的临床相关性及其对抗感染能力的潜在影响。