Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
Clin Exp Immunol. 2014 May;176(2):222-31. doi: 10.1111/cei.12268.
The purpose of the current study was to find novel rheumatoid arthritis (RA)-specific gene expression by simultaneously comparing the expression profiles of the synovial tissues from patients with RA, osteoarthritis (OA) and ankylosing spondylitis (AS). The Illumina Human HT-12 v4 Expression BeadChip was used to investigate the global gene expression profiles in synovial tissues from RA (n = 12), OA (n = 14) and AS (n = 7) patients. By comparing the profiles in synovial tissues from RA, OA and AS, we identified the CD38, ankyrin repeat domain 38 (ANKRD38), E2F transcription factor 2 (E2F2), craniofacial development protein 1 (CFDP1), cluster of differentiation (CD)7, interferon-stimulated exonuclease gene 20 kDa (ISG20) and interleukin-2 receptor gamma (IL)-2RG genes as differentially expressed gene expression in RA synovial tissues. The increased expression of CD38, E2F2 and IL-2RG, as revealed using real-time polymerase chain reaction (PCR) with synovial tissues from RA (n = 30), OA (n = 26) and AS patients (n = 20), was in agreement with the microarray data. Immunohistochemistry revealed significant CD38 expression and E2F2 in synovial membranes from RA patients (n = 5). The CD38(+) cells had high a percentage in the RA patients' blood (n = 103) and in the CD3(+) and CD56(+) subsets. The CD38(+) cell percentage was correlated significantly with RF level (P = 0·026) in RA patients. The IL-1α and IL-β levels were depressed significantly in the culture medium of RA synovial fibroblast cells (n = 5) following treatment with siRNAs targeting the E2F2 or CD38 genes. This study suggests that the uniquely increased expression of CD38 and E2F2 in RA synovial tissues contribute to the immunoactivation of the disease.
本研究的目的是通过同时比较类风湿关节炎（RA）、骨关节炎（OA）和强直性脊柱炎（AS）患者滑膜组织的表达谱，寻找新的 RA 特异性基因表达。我们使用 Illumina Human HT-12 v4 Expression BeadChip 来研究 RA（n=12）、OA（n=14）和 AS（n=7）患者滑膜组织的全基因表达谱。通过比较 RA、OA 和 AS 滑膜组织的表达谱，我们鉴定出 CD38、ankyrin repeat domain 38（ANKRD38）、E2F transcription factor 2（E2F2）、craniofacial development protein 1（CFDP1）、cluster of differentiation（CD）7、interferon-stimulated exonuclease gene 20kDa（ISG20）和 interleukin-2 receptor gamma（IL-2RG）是 RA 滑膜组织中差异表达的基因。使用实时聚合酶链反应（PCR）检测 RA（n=30）、OA（n=26）和 AS 患者（n=20）的滑膜组织，发现 CD38、E2F2 和 IL-2RG 的表达增加，与微阵列数据一致。免疫组织化学显示 RA 患者滑膜组织中 CD38 表达和 E2F2 明显增加（n=5）。RA 患者的血液（n=103）和 CD3+和 CD56+亚群中 CD38+细胞的比例较高。RA 患者中 CD38+细胞的比例与 RF 水平显著相关（P=0.026）。用靶向 E2F2 或 CD38 基因的 siRNA 处理 RA 滑膜成纤维细胞后，细胞培养基中 IL-1α 和 IL-β 水平显著降低（n=5）。本研究表明，RA 滑膜组织中 CD38 和 E2F2 的独特高表达有助于疾病的免疫激活。
