Increased CCL18 expression in patients with cutaneous T-cell lymphoma: association with disease severity and prognosis

Increased CCL18 expression in patients with cutaneous T-cell lymphoma: association with disease severity and prognosis
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DOI:
10.1111/j.1468-3083.2012.04495.x
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发表时间:
2013-01-01
影响因子:
9.2
通讯作者:
Sato, S.
Sato, S.
中科院分区:
医学2区
文献类型:
--
作者:
Miyagaki, T.;Sugaya, M.;Sato, S.

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背景CC趋化因子配体(CCL)18由单核细胞和树突状细胞(DCs)表达,对T细胞、B细胞和DCs具有强的趋化活性。CCL 18在特应性皮炎和大疱性类天疱疮皮损中表达上调,提示其在这些皮肤疾病的发生发展中起重要作用。目的探讨CCL 18在皮肤T细胞淋巴瘤(CTCL)中的作用。方法采用定量RT-PCR方法检测21例CTCL皮肤和7例正常皮肤中CCL 18 mRNA的表达。免疫组化法检测CCL 18的表达。采用酶联免疫吸附法检测38例CTCL患者和20例健康对照者血清CCL 18水平。我们还分析了血清CCL 18水平与其他临床和实验室数据之间的相关性。结果CTCL皮损中CCL 18 mRNA表达水平高于正常皮肤。CCL 18在CTCL皮肤中由真皮巨噬细胞和DC表达。CTCL患者血清CCL 18水平显著高于健康对照组,且与皮损类型相关。与改良严重加权评分、血清sIL-2 R、LDH、IL-4、IL-10、IL-31、CCL 17和CCL 26水平显著相关。血清CCL 18水平高的患者预后明显差于CCL 18水平低的患者。结论CTCL皮损中CCL 18 mRNA表达上调,血清CCL 18水平显著升高,且与CTCL的严重程度相关。这些结果表明,CCL 18可能与CTCL的发展。
Background CC chemokine ligand (CCL) 18 is expressed by monocytes and dendritic cells (DCs), and has potent chemotactic activity for T cells, B cells and DCs. CCL18 expression is up-regulated in lesional skin of atopic dermatitis and bullous pemphigoid, suggesting its important roles in the development of these skin diseases. Objective To investigate roles of CCL18 in cutaneous T-cell lymphoma (CTCL). Methods The CCL18 messenger RNA (mRNA) expression in CTCL skin (n = 21) and in normal skin (n = 7) was examined by quantitative RT-PCR. CCL18 expression was also examined by immunohistochemistry. Serum CCL18 levels were measured in 38 patients with CTCL and 20 healthy controls by enzyme-linked immunosorbent assay. We also analysed correlation between serum CCL18 levels and other clinical and laboratory data. Results The CTCL lesional skin contained higher levels of CCL18 mRNA than normal skin. CCL18 was expressed by dermal macrophages and DCs in CTCL skin. Serum CCL18 levels in patients with CTCL were significantly higher than those of healthy controls and correlated with types of skin lesions. They also significantly correlated with modified severity-weighted assessment scores, serum sIL-2R, LDH, IL-4, IL-10, IL-31, CCL17 and CCL26 levels. Patients with high serum levels of CCL18 showed significantly poor prognosis compared with those with low CCL18 levels. Conclusion CCL18 mRNA is up-regulated in CTCL lesional skin, and serum CCL18 levels are significantly increased and correlated with the severity of CTCL. These results suggest that CCL18 may be associated with the development of CTCL.