Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features.
Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features.
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DOI：
10.1186/ar3817
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发表时间：
2012-04-27
影响因子：
4.9
通讯作者：
Cañete JD
中科院分区：
文献类型：
--
作者：
Celis R;Planell N;Fernández-Sueiro JL;Sanmartí R;Ramírez J;González-Álvaro I;Pablos JL;Cañete JD
银屑病关节炎(PSA)是一种自身抗体阴性的免疫介导性疾病，发生滑膜淋巴新生(LN)。我们确定LN是否与成对滑膜组织(ST)和液体(SF)中炎性细胞因子表达的特定模式有关，以及它们与PSA临床特征的潜在相关性。ST和配对SF标本取自PSA患者发炎的膝关节。用CD3(T细胞)、CD20(B细胞)和MECA-79(高内皮血管)对ST进行免疫组织化学染色。提取总ST mRNA，用实时定量聚合酶链式反应检测21种T细胞来源和促炎性细胞因子的基因表达。Th1、Th2、Th17和促炎细胞因子的浓度用四抗体人Th17阵列测定。在纳入时和平均27个月的随访后收集临床和生物学数据。46例患者中有20例(43.5%)合并LN。LN阳性组与阴性组ST段差异仅有两个基因：白细胞介素23A(IL-23A)(P=0.058)和转化生长因子-β1(TGFR-β1)(P=0.050)。LN阳性患者IL-23A高表达，转化生长因子-β-1低表达。LN阳性患者ST IL-15m RNA表达无明显升高趋势，而SF IL-15蛋白表达水平显著升高(P=0.002)。在所有PSA患者中，IL-23AmRNA表达与C-反应蛋白(r=0.471；P=0.001)和关节肿胀计数(r=0.350；P=0.018)呈正相关，而SF水平与C反应蛋白(r=0.377；P=0.014和r=0.501；P<；0.0001)呈正相关。这些发现提示LN PSA患者的细胞因子谱存在差异，IL-23A和IL-15高表达，转化生长因子β1低表达。在整个患者组中，IL-23ST表达和CCL20SF水平与疾病活动性指标密切相关。这种细胞因子模式在LN阳性和阴性患者之间没有明显的临床或生物学差异。综上所述，这些结果提示IL-17/IL-23细胞因子轴在PSA滑膜LN中的作用。
Psoriatic arthritis (PsA) is an autoantibody-negative immune-mediated disease in which synovial lymphoid neogenesis (LN) occurs. We determined whether LN is associated with specific patterns of inflammatory cytokine expression in paired synovial tissue (ST) and fluid (SF) samples and their potential correlation with the clinical characteristics of PsA. ST and paired SF samples were obtained from the inflamed knee of PsA patients. ST samples were immunostained with CD3 (T cell), CD20 (B cell), and MECA-79 (high endothelial vessels). Total ST mRNA was extracted, and the gene expression of 21 T-cell-derived and proinflammatory cytokines were measured with quantitative real-time PCR. SF concentrations of Th1, Th2, Th17, and proinflammatory cytokines were determined with the Quantibody Human Th17 Array. Clinical and biologic data were collected at inclusion and after a median of 27 months of follow-up. Twenty (43.5%) of 46 patients had LN. Only two genes showed differences (Wilcoxon test, P < 0.06) in ST between LN-positive and LN-negative patients: interleukin-23A (IL-23A) (P = 0.058) and transforming growth factor-beta (TGF-β1) (P = 0.050). IL-23A expression was higher, and TGF-β1 expression was lower in LN-positive patients. ST IL-15 mRNA showed a nonsignificant trend toward higher expression in LN-positive patients, and SF IL-15 protein levels were significantly higher in LN-positive patients (P = 0.002). In all PsA patients, IL-23A mRNA expression correlated with C-reactive protein (CRP) (r = 0.471; P = 0.001) and swollen-joint count (SJC) (r = 0.350; P = 0.018), whereas SF levels of IL-6 and CC chemokine-ligand 20 (CCL-20) correlated with CRP levels (r = 0.377; P = 0.014 and r = 0.501; P < 0.0001, respectively). These findings suggest differences in the cytokine profile of PsA patients with LN, with a higher expression of IL-23A and IL-15 and a lower expression of TGF-β1. In the entire group of patients, IL-23 ST expression and CCL20 SF levels strongly correlated with markers of disease activity. This cytokine pattern was not accompanied by gross clinical or biologic differences between LN-positive and -negative patients. Taken together, these results suggest a role of the IL-17/IL-23 cytokine axis in synovial LN in PsA.
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影响因子：
4.9
作者：
Kruithof, Elli;Baeten, Dominique;De Rycke, Leen;Vandooren, Bernard;Foell, Dirk;Roth, Johannes;Canete, Juan D;Boots, Annemieke M;Veys, Eric M;De Keyser, Filip
通讯作者：
De Keyser, Filip
影响因子：
3.7
作者：
González-Álvaro I;Ortiz AM;Alvaro-Gracia JM;Castañeda S;Díaz-Sánchez B;Carvajal I;García-Vadillo JA;Humbría A;López-Bote JP;Patiño E;Tomero EG;Vicente EF;Sabando P;García-Vicuña R
通讯作者：
García-Vicuña R
影响因子：
--
作者：
Kane, D;Gogarty, M;FitzGerald, O
通讯作者：
FitzGerald, O
影响因子：
13.8
作者：
Robinson, Amanda;Kardos, Marisa;Kimball, Alexandra B.
通讯作者：
Kimball, Alexandra B.
影响因子：
--
作者：
Kraan, MC;Reece, RJ;Tak, PP
通讯作者：
Tak, PP