Association of CXCL10 and CXCL13 levels with disease activity and cutaneous manifestation in active adult-onset Still's disease
Association of CXCL10 and CXCL13 levels with disease activity and cutaneous manifestation in active adult-onset Still's disease
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DOI：
10.1186/s13075-015-0773-4
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发表时间：
2015-09-19
影响因子：
4.9
通讯作者：
Kim, Hyoun-Ah
中科院分区：
文献类型：
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作者：
Han, Jae Ho;Suh, Chang-Hee;Kim, Hyoun-Ah
简介：C-X-C基序趋化因子10（CXCL 10）响应于干扰素-γ而产生，并且肿瘤坏死因子-α（TNF-α）触发活化的淋巴细胞的积累。CXCL 13在次级淋巴组织中组成型表达，并且表达通过T细胞刺激被TNF-α上调。CXCL 10和CXCL 13在成人型斯蒂尔病（AOSD）的发病中可能起着重要作用，因此，我们研究了CXCL 10和CXCL 13在活动性AOSD患者中的表达水平与临床表现的关系。在AOSD患者中，从15 9.6 +/- 9.2个月后收集随访样本。采用酶联免疫吸附法测定血清CXCL 10和CXCL 13水平。通过免疫组化检测26例AOSD患者皮损活检标本中CXCL 10、CXCL 13和C-X-C趋化因子受体3（CXCR 3）的表达水平。AOSD患者的CXCL 10水平（1，031.3 +/-2，019.6 pg/mL）高于RA（146.3 +/- 91.4 pg/mL，p = 0.008）和HC（104.4 +/- 47.9 pg/mL，p = 0.006）。此外，AOSD患者的CXCL 13水平（158.8 +/-151.2pg/mL）高于RA（54.4 +/-61.1pg/mL，p < 0.001）和HC（23.5 +/-18.1pg/mL，p < 0.001）。血清CXCL 10水平与铁蛋白和全身评分相关。血清CXCL 13水平与血红蛋白、C-反应蛋白、铁蛋白和白蛋白以及系统评分相关。在随访的AOSD患者中，CXCL 10和CXCL 13水平显著下降（分别为153.7 +/- 130.1 pg/mL，p = 0.002和89.1 +/- 117.4 pg/mL，p = 0.001）。在免疫组织化学上，表达CXCL 10的炎性细胞的百分比范围为1 - 85%，CXCL 13为1 - 72%，CXCR 3为2 - 65%。CXCL 10阳性炎性细胞的百分比在表现出粘蛋白沉积的皮肤活检样品中高于那些没有表现出粘蛋白沉积的皮肤活检样品（p = 0.01）。结论：血清CXCL 10和CXCL 13水平可作为AOSD患者病情活动性评估的临床指标。CXCL 10/CXCR 3和CXCL 13可能有助于AOSD中的炎症反应，特别是其皮肤表现。
Introduction: C-X-C motif chemokine 10 (CXCL10) is produced in response to interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha) triggers the accumulation of activated lymphocytes. CXCL13 is constitutively expressed in secondary lymphoid tissues, and the expression is upregulated by TNF-alpha, via T cell stimulation. It appears that CXCL10 and CXCL13 could play a potential role in the pathogenesis of adult-onset Still's disease (AOSD), therefore, we investigated the associations between CXCL10 and CXCL13 levels and clinical manifestations in patients with active AOSD.Methods: Blood samples were collected from 39 active AOSD patients, 32 rheumatoid arthritis (RA) patients and 40 healthy controls (HC). Of the AOSD patients, follow-up samples were collected from 15 9.6 +/- 9.2 months later. Serum levels of CXCL10 and CXCL13 were determined using enzyme-linked immunosorbent assay. CXCL10, CXCL13, and C-X-C chemokine receptor type 3 (CXCR3) expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes were investigated via immunohistochemistry.Results: The CXCL10 levels in AOSD patients (1,031.3 +/- 2,019.6 pg/mL) were higher than in RA (146.3 +/- 91.4 pg/mL, p = 0.008) and HC (104.4 +/- 47.9 pg/mL, p = 0.006). Also, the CXCL13 levels of AOSD patients (158.8 +/- 151.2 pg/mL) were higher than those of RA (54.4 +/- 61.1 pg/mL, p < 0.001) and HC (23.5 +/- 18.1 pg/mL, p < 0.001). Serum CXCL10 levels correlated with ferritin and systemic scores. Serum CXCL13 levels correlated with those of hemoglobin, C-reactive protein, ferritin, and albumin, and systemic scores. In follow-up AOSD patients, the levels of CXCL10 and CXCL13 fell significantly (153.7 +/- 130.1 pg/mL, p = 0.002, and 89.1 +/- 117.4 pg/mL, p = 0.001, respectively). On immunohistochemistry, the percentages of inflammatory cells expressing CXCL10 ranged from 1 to 85 %, CXCL13 from 1 to 72 %, and CXCR3 from 2 to 65 %. The percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples exhibiting mucin deposition than in those that did not (p = 0.01). CXCL13 levels were correlated with those of CD4 and CD68.Conclusions: Serum CXCL10 and CXCL13 levels may serve as clinical markers for assessment of disease activity in AOSD. CXCL10/CXCR3 and CXCL13 may contribute to the inflammatory response, especially skin manifestations thereof, in AOSD.