目的 了解强直性脊柱炎病人关节液单核细胞（SFMC）基因的变化及其特点， 探讨与AS关节炎发生相关的基因及可能的意义。方法 采用含1176个基因cDNA微阵列检测5例AS，6例健康人和5例RA病人的基因表达，挑选其中9个AS SFMC表达异常的致炎，抗炎，信息传导基因或受体和黏附分子，扩大例数以半定量PCR再验证微阵列检测结果。结果 cDNA微阵列和PCR结果显示，AS的SFMC 1176基因图谱和阳性基因数量在RA和AS病人组无明显区别；比较AS或RA病人的SFMC和PBMC，则显示AS和RA的SFMC中的阳性基因均少于各自的PBMC；在RA的PBMC有53个基因明显高于RA SFMC（P<0.05），但在AS PBMC仅有5个基因明显高于AS SFMC（P<0.05）。AS病人SFMC的IL-1β，TNF-a；TGF-β，TGF-β2；c-jun， JAK-3显著高于健康人PBMC（p<0.05）。结论 AS患者的SFMC基因表达谱异常，但与RA的SFMC未见明显特征型区别，IL-1β，TNF-a；TGF-β，TGF-β2；c-jun JAK-3与AS关节炎的发生和发展相关。

Objectives. To test in a large open study whether thalidomide is potentially useful in treating ankylosing spondylitis, and to see if thalidomide induces any change in expression of genes in peripheral blood mononuclear cells (PBMC). Methods. Thirty male patients with treatment-refractory ankylosing spondylitis were recruited into a 12-month open study using thalidomide at a dosage of 200mg/day. Seven indices were measured as primary outcome measures, and 6 other indices as secondary outcome measures. Transcripts in the PBMC of some of these patients were first screened with microarray, and then measured with reverse transcriptase-polymerase chain reaction. Results. Twenty-six patients completed the study. Of these, 80% showed a >20% improvement in 4 of 7 primary indices. Sharp declines in several parameters were noticed at 3-6 months. Nine patients became pain-free. There was also a statistically significant decrease in tumor necrosis factor α transcripts in the PBMC. Conclusion. Thalidomide is a reasonably promising drug in treatment-resistant ankylosing spondylitis.

Objective. To use gene expression profiles of spondyloarthropathy (SpA) synovial fluid mononuclear cells (SFMC) to determine if there are transcripts that support the unfolded protein response (UPR) hypothesis, and to identify which cytokines/chemokines are being expressed and which cell fractions are involved. Methods. Gene expression profiles were generated by microarray screening of SFMC of 5 patients with SpA, 5 patients with rheumatoid arthritis (RA), and peripheral blood mononuclear cells (PBMC) of 6 controls. Results were validated by reverse transcription polymerase chain reaction using samples from a larger panel of subjects. Results. The repertoires of proinflammatory cytokines/chemokines expressed by SpA and RA SFMC were very similar: monocyte chemotractant protein 1 (MCP-1), interleukin 8 (IL-8), IL-1ß, endothelial-monocyte activating polypeptide Ⅱ, interferon-γ, and tumor necrosis factor-α. MCP-1 was highly expressed in SpA SFMC. There was enhanced expression of immunoglobulin heavy chain binding protein (BiP) in SpA, which is compatible with the UPR hypothesis. BiP was most highly expressed in the adherent fraction of SpA SFMC. Conclusion. Previous data postulating UPR in SpA are based on in vitro experiments with transfected cell lines. Our patient derived data suggest that it also occurs in vivo in the macrophages of SpA joints. (J Rheumatol 2002; 29: 2159-64)

目的 了解强直性脊柱炎（AS）患者外周血单个核细胞（PBMC）基因表达谱与类风湿关节炎（RA）及健康志愿者有无差异，寻找疾病发生及炎症相关的异常变化基因，初步探讨其变化意义。方法 以含588个基因的cDNA微阵列检测7例活动期AS、6例活动期RA患者以及7例健康志愿者PBMC基因表达谱，并挑选至少有4例关节炎患者表达增多的13个炎症反应相关的细胞因子，扩大研究病例数以半定量RT-PCR方法验证其表达水平。结果 cDNA微阵列检测结果显示，AS和RA患者基因表达谱明显异常。在健康志愿者组，AS和RA患者的异常高表达的基因表达率分别为8.4%，32.5%和44.8%，两组关节炎患者与健康志愿者P均<0.001；而且RA组异常表达率又明显多于AS组（P<0.012），2例活动性肺结核患者也有类似的高表达。以RT-PCR法验证的13个基因的表达水平，发现22例AS，8例RA患者基因表达结果与cDNA微阵列检测结果一致。结论 AS患者PBMC基因表达谱明显异常，与RA患者也显著不同，13个细胞因子的高表达对AS无特异性。