Generation of Antibodies of Distinct Subclasses and Specificity Is Linked to H2s in an Active Mouse Model of Epidermolysis Bullosa Acquisita
Generation of Antibodies of Distinct Subclasses and Specificity Is Linked to H2s in an Active Mouse Model of Epidermolysis Bullosa Acquisita
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DOI：
10.1038/jid.2010.248
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发表时间：
2011-01-01
影响因子：
6.5
通讯作者：
Ibrahim, Saleh M.
中科院分区：
文献类型：
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作者：
Ludwig, Ralf J.;Recke, Andreas;Ibrahim, Saleh M.
获得性大疱性表皮病（EBA）是一种自身免疫性起泡性疾病，其特征在于VII型胶原（COL 7）抗体。EBA可以通过用鼠COL 7的非胶原1结构域的片段免疫在小鼠中诱导。与其他自身免疫性疾病相反，E。例如，在一个实施例中，在类风湿性关节炎中，对EBA的遗传易感性知之甚少。因此，我们使用EBA小鼠模型来解决疾病诱导依赖于主要组织相容性复合体（MHC）单倍型的假设。用重组小鼠COL 7免疫来自不同近交系的小鼠。观察到五种不同的反应：诱导（i）SJL/J（H2s）和雌性MRL/MpJ（H2k）中的重度疾病，（ii）C57 B1/10.s（H2s）中的轻度和短暂疾病，（iii）DBA/1 J（H2 q）中的显微镜下水泡，（iv）C57 B1/6 J（H2 b）、NZM 2410/J（H2 z）、BXD 2（H2 b）和雄性MRL/MpJ中仅存在非致病性自身抗体，和（v）在NOD/ShiLtJ（H2 g7）和C57 Bl/10.q（H2 q）小鼠中对EBA的完全抗性。总体而言，EBA的易感性与H2S密切相关。此外，患病表型与针对COL 7特定区域的自身抗体相关。我们的研究结果表明，诱导抗体与一个独特的特异性是联系在一起的MHC单倍型实验EBA。此外，我们的数据是未来研究的基础，目的是确定非MHC EBA易感基因。
Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease, characterized by antibodies to type VII collagen (COL7). EBA can be induced in mice by immunization with a fragment of the non-collagenous 1 domain of murine COL7. Contrary to other autoimmune diseases, e. g., rheumatoid arthritis, little is known about the genetic susceptibility for EBA. We therefore used the EBA mouse model to address the hypothesis that disease induction depends on the major histocompatibility complex (MHC) haplotype. Mice from different inbred strains were immunized with recombinant murine COL7. Five distinct responses were observed: induction of (i) severe disease in SJL/J (H2s) and female MRL/MpJ (H2k), (ii) mild and transient disease in C57Bl/10.s (H2s), (iii) microscopic blistering in DBA/1J (H2q), (iv) only presence of non-pathogenic autoantibodies in C57Bl/6J (H2b), NZM2410/J (H2z), BXD2 (H2b), and male MRL/MpJ, and (v) complete resistance to EBA in NOD/ShiLtJ (H2g7) and C57Bl/10.q (H2q) mice. Overall, susceptibility to EBA was strongly associated with H2s. In addition, the diseased phenotype was associated with autoantibodies to specific regions of COL7. Our findings show that induction of antibodies with a distinct specificity is linked to the MHC haplotype in experimental EBA. Furthermore, our data are the basis for future studies with the goal of identifying non-MHC EBA susceptibility genes.