Expression of MHC class I dimers and ERAP1 in an ankylosing spondylitis patient cohort
Expression of MHC class I dimers and ERAP1 in an ankylosing spondylitis patient cohort
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DOI：
10.1111/j.1365-2567.2011.03453.x
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发表时间：
2011-07-01
期刊：
影响因子：
6.4
通讯作者：
Powis, Simon J.
中科院分区：
文献类型：
--
作者：
Campbell, Elaine C.;Fettke, Franziska;Powis, Simon J.
人类白细胞抗原HLA-B27与强直性脊柱炎密切相关，强直性脊柱炎是一种血清阴性的炎性关节炎。在这项研究中，与疾病发病机制的几个假设方面进行了调查。将来自29名强直性脊柱炎患者和1名反应性关节炎患者的小型患者队列的血液单核细胞来源的树突状细胞（DC）与来自34名健康对照受试者的DC进行比较，其中4名被发现为HLA-B27阳性。检测HLA-B27形成与单克隆抗体HC 10反应的重链二聚体的能力，沿着诱导内质网（ER）应激，通过剪接xbp 1 mRNA和免疫印迹法测定免疫球蛋白结合蛋白（BiP）。此外，ER常驻氨基肽酶基因ERAP 1的蛋白表达水平在强直性脊柱炎患者也被确定，其最近被鉴定为一种新的疾病相关基因。在患者或对照DC群体中形成的HC 10反应性MHC I类二聚体的总体水平没有显著差异。通过xbp 1 mRNA剪接测定，未检测到ER上的应力，但在患者DC中观察到较低水平的BiP。进一步潜在的兴趣是，在该患者队列中，与对照相比，ERAP 1的表达在许多患者DC样品中似乎更高，表明ERAP 1的过表达是促进强直性脊柱炎发病机制的机制。
P>The human leucocyte antigen HLA-B27 is strongly associated with ankylosing spondylitis, a form of seronegative inflammatory arthritis. In this study aspects related to several hypothesized mechanisms of disease pathogenesis have been investigated. Blood monocyte-derived dendritic cells (DC) from a small patient cohort of 29 patients with ankylosing spondylitis and one with reactive arthritis, were compared with DC from 34 healthy control subjects, of whom four were found to be HLA-B27 positive. The ability of HLA-B27 to form heavy-chain dimers reactive with monoclonal antibody HC10 was tested, along with the induction of endoplasmic reticulum (ER) stress, assessed by splicing xbp1 mRNA and immunoblotting of Immunoglobulin Binding Protein (BiP). Additionally, the protein expression levels of the ER resident aminopeptidase gene ERAP1 in patients with ankylosing spondylitis was also determined, following its recent identification as a novel disease-associated gene. No significant difference was noted in the global levels of HC10-reactive MHC class I dimers formed in either the patient or control DC populations. Stress on the ER, as determined by xbp1 mRNA splicing, was not detected but lower levels of BiP were observed in the DC from patients. Of further potential interest, in this patient cohort the expression of ERAP1 appeared to be higher in a number of patient DC samples when compared with controls, suggesting over-expression of ERAP1 as a mechanism promoting ankylosing spondylitic pathogenesis.