目的通过比较强直性脊柱炎（AS）患者和健康志愿者的基因表达谱，寻找与AS相关的新基因并探讨其在病因和发病机制中的意义。方法 用含588个基因的cDNA微阵列，检测AS和健康志愿者的外周血单个核细胞的基因表达谱，初步筛选出在AS中差异表达的基因，为了进一步验证cDNA微阵列差异表达基因结果，扩大各组病例数，再用RT-PCR技术同时检测、对比健康志愿者和AS患者外周血单个核细胞（PBMC）、关节液单个核细胞（SFMC）和关节滑膜细胞这些差异表达基因的变化。结果 和健康志愿者组的PBMC比较，AS病人的MNDA、迁移抑制因子相关蛋白8（MRP8）和MRP14、粘附分子ICAM-1和Integrinβ1表达明显增高，其中MNDA和MRP8的变化相关系数为0.793。在AS的SFMC和关节滑膜细胞中，MNDA表达也显著增高（与健康志愿者组PBMC比较，P值分别为0.038和0.027）；MNDA区别AS和健康志愿者的统计学鉴别准确率达1。AS病人在接受抗TNF-α单克隆抗体治疗3个月后，MNDA在关节滑膜细胞的表达水平显著下降（P=0.018）。结论 MNDA是AS发病过程中一个重要的并与单核/巨噬细胞致炎密切相关的免疫因子，可能成为一种用于AS的诊断、治疗监控指标。

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。

目的 过去的研究发现，将HLA-B27基因转入Hela细胞可使信息传递发生变化，单核细胞趋化蛋白1（MCP-1）的表达增加。本研究旨在通过检测强直性脊柱炎（AS）病人的外周血单个核细胞（PBMC）、关节滑液单个核细胞（SFMC）和滑膜细胞趋化因子MCP基因表达水平，了解它们在AS中的变化及其在关节炎发病机制中的作用和意义。方法 健康志愿者和AS病人的PBMC基因表达谱通过含1176基因的cDNA微阵列扫描结果得到，筛选出的差异表达基因再以RT-PCR方法验证AS病人PBMC、关节滑液SFMC、AS滑膜中的表达水平。结果 MCP-1在AS患者SFMC表达明显高于健康志愿者的PBMC和AS病人的PBMC。AS患者SFMC中MCP-1水平与MCP-3水平呈正相关（r=0.76，P=0.003）；MCP-1在AS患者的关节滑膜细胞的表达水平明显高于健康对照者的关节滑膜细胞（P值为0.0035）；LPS刺激4小时后，AS患者和健康志愿者的外周血单核细胞的MCP-1的表达显著增高。结论 MCP-1在AS病人SFMC和关节滑膜细胞中呈高表达，提示MCP-1可能在AS病人的炎症细胞向关节的归巢以及关节局部的炎症反应中起重要作用。

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 identify genes which are more highly expressed in the peripheral blood mononuclear cells (PBMC) of patients with spondyloarthropathy (SpA), rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in comparison to normal subjects. Methods. A 558-gene microarray was used as a screening tool to select a panel of such genes from PBMC of these subjects and of normal subjects. Results were then validated by reverse transcription-polymerase chain reaction (TR-PCR). Results. The following genes were more highly expressed in arthritis patients than in normal subjects: macrophage differentiation marker MNDA (myeloid nuclear differentiation antigen), MRP8 and MRP14 (migratory inhibitory factor-related proteins); signaling molecules JAK3 (janus kinase 3) and MAP kinase p38 (mitogen-activated protein kinase); receptors TNFR2/p75, CCR1, CXCR4 and integrin β1; and the cytokines/chemokines interleukin (IL)1 β AND IL-8. Expression of CXCR4 was unexpectedly high among all arthritis subjects. Using RT-PCR, ELISA and immunohistology, expression of stromal cell-derived factor 1(SDF-1) was demonstrated in arthritis joints.

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.

目的：通过比较强直性脊柱炎（AS）病人抗TNF-α单克隆抗体Remicade治疗前后的膝关节滑膜细胞的基因谱变化，找出缓解AS病情相关的主要基因金属蛋白酶3（MMP-3），并探讨MMP-3的调控潜在的作用和在AS关节炎发病中的作用机制和意义。方法：从AS病人在Remicade治疗前和治疗3个月后的关节滑膜细胞的基因表达谱（用含1176基因的cDNA微阵列检测）结果中筛选的靶基因即差异表达最显著的MMP-3为特异性刺激因子，用RT-PCR方法检测它诱导健康志愿者外周血单个核细胞（PBMC）的炎症相关基因TNF-α、c-jun和c-fos的表达。结果：比较AS病人治疗前后的关节滑膜细胞基因差异表达的结果，MMP-3治疗后下调最显著（P=0.0147）。与MMP-3聚类在一起的基因有111个，和 MMP-3相关性最强的基因是金属蛋白酶抑制剂前体-1（TIMP-1）；MMP-3能显著诱导外周血单个核细胞（PBMC）的TNF-α、c-jun和c-fos的表达。结论：在Remicade 治疗AS过程中，下调MMP-3是最重要的环节之一；通过检测MMP-3在关节滑膜细胞组织中的表达水平可作为AS诊断和病情进展监控的参考指标；MMP-3下调，可能使TNF-TNFR2-JNK-AP-1信息通道的激活状态减弱，从而减少致炎因子的释放，调整异常的基质降解和血管形成等病理因素，缓解AS炎症、减少软骨和骨质破坏的作用。