Carulli M T, Handler C, Coghlan J G, Black C M, Denton C P
Centre for Rheumatology, Royal Free and University College Medical School, Rowland Hill Street, Hampstead, London, NW3 2PF, UK.
Ann Rheum Dis. 2008 Jan;67(1):105-9. doi: 10.1136/ard.2006.067967. Epub 2007 Jun 29.
The chemokine CCL2 has been consistently found to be up-regulated in systemic sclerosis. To explore the potential value of serum CCL2 measurement in disease assessment, we have compared CCL2 levels with clinical phenotype and investigated effect of therapy on circulating CCL2.
Serum samples from a well characterised cohort of 94 systemic sclerosis (SSc) patients, 16 patients with primary Raynaud phenomenon and 11 healthy controls were examined by ELISA. Our cohort of patients included 50 patients with limited cutaneous (lc)SSc (20 with lcSSc alone and 30 with pulmonary arterial hypertension-lcSSc), and 44 with diffuse cutaneous (dc)SSc, 30 of which had early-onset dcSSc.
Serum levels of CCL2 were increased in both major SSc subsets. In early stage dcSSc 18/30 (60%) cases demonstrated markedly elevated CCL2, and this was associated with anti-topoisomerase or anti-RNA polymerase I/III antibody reactivity, and with greater frequency of major organ-based complications. Elevation of CCL2 serum levels in the lcSSc subset was not associated with pulmonary arterial hypertension, although there was a trend for reduction following treatment with prostacyclin analogues or bosentan.
These findings suggest that the CCL2/CCR2 axis is a potential therapeutic target in SSc, particularly in the early dcSSc subset. CCL2 measurement may be useful for risk stratification in early stage disease, but its value in disease monitoring is questionable.
一直以来发现趋化因子CCL2在系统性硬化症中上调。为了探索血清CCL2检测在疾病评估中的潜在价值，我们比较了CCL2水平与临床表型，并研究了治疗对循环CCL2的影响。
采用酶联免疫吸附测定法检测了来自94例系统性硬化症（SSc）患者、16例原发性雷诺现象患者和11名健康对照者的血清样本。我们的患者队列包括50例局限性皮肤（lc）SSc患者（20例仅为lcSSc，30例合并肺动脉高压-lcSSc），以及44例弥漫性皮肤（dc）SSc患者，其中30例为早发型dcSSc。
两个主要的SSc亚组中CCL2血清水平均升高。在早发型dcSSc中，18/30（60%）的病例显示CCL2显著升高，这与抗拓扑异构酶或抗RNA聚合酶I/III抗体反应性相关，并且主要器官并发症的发生率更高。lcSSc亚组中CCL2血清水平升高与肺动脉高压无关，尽管使用前列环素类似物或波生坦治疗后有下降趋势。
这些发现表明CCL2/CCR2轴是SSc的一个潜在治疗靶点，特别是在早发型dcSSc亚组中。CCL2检测可能有助于疾病早期的风险分层，但其在疾病监测中的价值值得怀疑。
