Galligan C L, Baig E, Bykerk V, Keystone E C, Fish E N
Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
Gene expression profiling of rheumatoid arthritis (RA) and osteoarthritis (OA) joint tissue samples provides a unique insight into the gene signatures involved in disease development and progression. Fibroblast-like synovial (FLS) cells were obtained from RA, OA and control trauma joint tissues (non-RA, non-OA) and RNA was analyzed by Affymetrix microarray. Thirty-four genes specific to RA and OA FLS cells were identified (P<0.05). HOXD10, HOXD11, HOXD13, CCL8 and LIM homeobox 2 were highly and exclusively expressed in RA and CLU, sarcoglycan-gamma, GPR64, POU3F3, peroxisome proliferative activated receptor-gamma and tripartite motif-containing 2 were expressed only in OA. The data also revealed expression heterogeneity for patients with the same disease. To address disease heterogeneity in RA FLS cells, we examined the effects of clinical disease parameters (Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF)) and drug therapies (methotrexate/prednisone) on RA FLS cell gene expression. Eight specific and unique correlations were identified: human leukocyte antigen (HLA)-DQA2 with HAQ score; Clec12A with RF; MAB21L2, SIAT7E, HAPLN1 and BAIAP2L1 with CRP level; RGMB and OSAP with ESR. Signature RA FLS cell gene expression profiles may provide insights into disease pathogenesis and have utility in diagnosis, prognosis and drug responsiveness.
类风湿关节炎（RA）和骨关节炎（OA）关节组织样本的基因表达谱分析为了解疾病发生发展过程中涉及的基因特征提供了独特视角。从RA、OA以及对照创伤关节组织（非RA、非OA）中获取成纤维样滑膜（FLS）细胞，并通过Affymetrix微阵列分析RNA。鉴定出34个RA和OA FLS细胞特有的基因（P<0.05）。HOXD10、HOXD11、HOXD13、CCL8和LIM同源框2在RA中高度且特异性表达，而CLU、肌聚糖-γ、GPR64、POU3F3、过氧化物酶体增殖物激活受体-γ和含三联基序蛋白2仅在OA中表达。数据还揭示了同一种疾病患者的表达异质性。为了研究RA FLS细胞中的疾病异质性，我们检测了临床疾病参数（健康评估问卷（HAQ）评分、C反应蛋白（CRP）、红细胞沉降率（ESR）、类风湿因子（RF））和药物治疗（甲氨蝶呤/泼尼松）对RA FLS细胞基因表达的影响。确定了8种特异性且独特的相关性：人类白细胞抗原（HLA）-DQA2与HAQ评分；Clec12A与RF；MAB21L2、SIAT7E、HAPLN1和BAIAP2L1与CRP水平；RGMB和OSAP与ESR。特征性的RA FLS细胞基因表达谱可能有助于深入了解疾病发病机制，并在诊断、预后和药物反应性方面具有应用价值。
