Rihl Markus, Kellner Herbert, Kellner Wolfgang, Barthel Christian, Yu David T Y, Tak Paul P, Zeidler Henning, Baeten Dominique
Hannover Medical School, Hannover, Germany.
Arthritis Rheum. 2008 Nov;58(11):3430-5. doi: 10.1002/art.23998.
Understanding of the molecular pathophysiology of spondylarthritis (SpA) remains largely elusive. This is related both to the complexity of the disease (axial versus peripheral disease, inflammation versus tissue remodeling) and to the difficulty in obtaining samples from primary disease sites. This study was undertaken to explore a gene expression approach for identifying novel candidate mediators of SpA.
Sacroiliac joint fluid aspirates from 3 SpA patients with active sacroiliitis were studied by microarray analysis. The expression of selected candidate molecules in peripheral synovitis was confirmed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay.
Microarray analysis identified 4 sacroiliitis gene clusters, containing a total of 47 messenger RNA (mRNA) transcripts. Two clusters contained genes expressed in all sacroiliitis samples, corresponding to both known and unsuspected candidate mediators of SpA pathology. These included proinflammatory molecules as well as molecules involved in tissue remodeling, such as transforming growth factor beta2. Of the novel candidate genes selected for confirmation, interleukin-7 (IL-7) mRNA expression was higher in SpA peripheral synovial fluid and synovial tissue samples than in osteoarthritis samples, and similar to expression in rheumatoid arthritis (RA) samples. At the protein level, synovial fluid IL-7 levels were even higher in SpA than in RA, despite lower levels of tumor necrosis factor alpha and IL-1beta.
In the present study, both known and unsuspected candidate mediators of SpA pathogenesis were identified, including IL-7. The specific overexpression of IL-7 at sites of peripheral synovitis in SpA suggests that further functional investigations of the role of this cytokine in SpA pathogenesis are warranted.
对脊柱关节炎（SpA）分子病理生理学的理解在很大程度上仍然不清楚。这既与疾病的复杂性（轴向与外周疾病、炎症与组织重塑）有关，也与从原发性疾病部位获取样本的困难有关。本研究旨在探索一种基因表达方法来识别SpA的新型候选介质。
通过微阵列分析研究了3例患有活动性骶髂关节炎的SpA患者的骶髂关节液抽吸物。通过逆转录聚合酶链反应和酶联免疫吸附测定法确认了外周滑膜炎中选定候选分子的表达。
微阵列分析确定了4个骶髂关节炎基因簇，共包含47种信使核糖核酸（mRNA）转录本。两个簇包含在所有骶髂关节炎样本中表达的基因，对应于SpA病理已知和未被怀疑的候选介质。这些包括促炎分子以及参与组织重塑的分子，如转化生长因子β2。在选择用于确认的新型候选基因中，白细胞介素-7（IL-7）mRNA在SpA外周滑液和滑膜组织样本中的表达高于骨关节炎样本，与类风湿关节炎（RA）样本中的表达相似。在蛋白质水平上，尽管肿瘤坏死因子α和IL-1β水平较低，但SpA滑液中IL-7水平甚至高于RA。
在本研究中，确定了SpA发病机制的已知和未被怀疑的候选介质，包括IL-7。SpA外周滑膜炎部位IL-7的特异性过表达表明，有必要对这种细胞因子在SpA发病机制中的作用进行进一步的功能研究。
