Autoreactive antibodies are present in sheep with Johne's disease and cross-react with Mycobacterium avium subsp paratuberculosis antigens
Autoreactive antibodies are present in sheep with Johne's disease and cross-react with Mycobacterium avium subsp paratuberculosis antigens
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DOI：
10.1016/j.micinf.2007.03.016
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发表时间：
2007-07-01
影响因子：
5.8
通讯作者：
Griffin, J. Frank T.
中科院分区：
文献类型：
--
作者：
Berger, Sven;Bannantine, John P.;Griffin, J. Frank T.
在临床研究和小动物模型中，分枝杆菌感染与自身抗体的产生有关，包括抗中性粒细胞胞质自身抗体（ANCA）。在自然感染的反刍动物中，试图鉴定与自身抗原和分枝杆菌抗原反应的抗体。我们产生了包含来自患有约翰氏病（JD）的绵羊的单链抗体片段（scFv）的噬菌体展示文库。同时对绵羊小肠组织和鸟分枝杆菌亚种进行筛选。副结核病（MAP）。一个克隆（称为AutoH 1）与宿主组织和MAP反应强烈，识别绵羊肠道组织和消化道中的蛋白酶敏感的32 kDa决定簇。并且在血液粒细胞中而不是单核细胞中。在粒细胞中，结合是细胞质颗粒和细胞膜;在MAP中。AutoH 1结合细菌细胞壁决定簇。我们进一步鉴定了AutoH 1识别的合成肽序列，并以此合成了载体-肽融合蛋白（paH 1），筛选了正常和JD绵羊血清中的AutoH 1样自身抗体活性，7/11只JD动物显示出可被paH 1阻断的自身反应性，0/21只正常动物显示出无此类血清学反应性。在反刍动物JD中观察到的严重病理可能具有自身免疫成分，可能是由于ANCA型结合所致;这仍有待进一步研究。(c)2007年，Elsevier Masson SAS。All rights reserved.
Mycobacterial infection has been linked to the generation of autoantibodies, including anti-neutrophil cytoplasmic autoantibodies (ANCA), in clinical studies and small animal models. In an attempt to identify antibodies that react with both self and mycobacterial antigens in naturally infected ruminants. we generated a phage display library comprising single chain antibody fragments (scFv) from sheep with Johne's disease (JD). The library was screened simultaneously against ovine small intestinal tissue and Mycobacterium avium subsp. paratuberculosis (MAP). A clone (termed AutoH1) reacted strongly with host tissue and MAP, recognizing a proteinase-susceptible 32 kDa determinant in ovine gut tissues and lymphatics. and in blood granulocytes but not mononuclear cells. In granulocytes, binding was to cytoplasmic granules and cell membranes; in MAP. AutoH1 bound bacterial cell wall determinants. We further identified a synthetic peptide sequence recognized by AutoH1, using this to generate a carrier:peptide fusion protein (paH1).Sera of normal and JD sheep were screened for AutoH1-like autoantibody activity; 7/11 JD animals showed autoreactivity that could be blocked by paH1, while 0/21 normal animals showed no such serological reactivity. It is possible that the severe pathology observed in ruminant JD may have an autoimmune component, possibly due to ANCA-type binding; this remains to be further investigated. (c) 2007 Elsevier Masson SAS. All rights reserved.