HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta(2)-microglobulin (beta(2)m) double transgenic mice with disrupted mouse beta(2)m
HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta(2)-microglobulin (beta(2)m) double transgenic mice with disrupted mouse beta(2)m
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DOI：
10.1172/jci119100
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发表时间：
1996-12-15
影响因子：
15.9
通讯作者：
David, CS
中科院分区：
文献类型：
--
作者：
Khare, SD;Hansen, J;David, CS
MHC I类等位基因HLA-B27与一组称为脊柱关节病的人类疾病密切相关。其中一些疾病在肠道或泌尿生殖道感染后发病。在本研究中，我们描述了HLA-B27转基因小鼠的自发性疾病，其中内源性β（2）-微球蛋白（β（2）m）基因被替换为转基因人β（2）m基因。这些小鼠显示出与人外周血单核细胞相似的HLA-B27的细胞表面表达。此外，HLA-B27的游离重链（HC）也在胸腺上皮和表达B27的PBL的亚群上表达。这些小鼠在后爪中发展出自发性关节炎和指甲变化，关节炎主要发生在雄性动物中，只有当小鼠从无病原体屏障设施转移到常规区域时，转基因小鼠表达HLA-B27与小鼠β（2）m在细胞表面上有不可检测的游离HC水平，不会发展关节炎。在体内治疗与抗HC特异性抗体延迟发病，我们的数据表明，HLA-B27 '自由' HCB的疾病过程中的具体参与。
MHC class I allele, HLA-B27, is strongly associated with a group of human diseases called spondyloarthropathies. Some of these diseases have an onset after an enteric or genitourinary infection. In the present study, we describe spontaneous disease in HLA-B27 transgenic mice where endogenous beta(2)-microglobulin (beta(2)m) gene was replaced with transgenic human beta(2)m gene. These mice showed cell surface expression of HLA-B27 similar to that of human peripheral blood mononuclear cells, In addition, free heavy chains (HCs) of HLA-B27 were also expressed on thymic epithelium and on a subpopulation of B27-expressing PBLs, These mice developed spontaneous arthritis and nail changes in the rear paws, Arthritis occurred primarily in male animals and only when mice were transferred from the pathogen-free barrier facility to the conventional area, Transgenic mice expressing HLA-B27 with mouse beta(2)m have undetectable levels of free HCs on the cell surface and do not develop arthritis. In vivo treatment with anti-HC-specific antibody delayed the onset of disease, Our data demonstrate specific involvement of HLA-B27 'free' HCB in the disease process.