Pacini Greta, Cavalli Giulio, Tomelleri Alessandro, De Luca Giacomo, Pacini Guido, Ferrarini Marina, Doglioni Claudio, Dagna Lorenzo
Unit of Immunology, Rheumatology, Allergy, and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Oncoimmunology. 2018 Mar 15;7(7):e1440929. doi: 10.1080/2162402X.2018.1440929. eCollection 2018.
Erdheim-Chester disease (ECD) is a rare histiocytosis, characterized by xanthogranulomatous tissue infiltration by foamy histiocytes. Fibrosis, a histologic hallmark of ECD, is responsible for lesion growth and clinical manifestations. Unraveling molecular fibrotic pathway in ECD would allow the identification of new pharmacologic targets. In this study, we evaluated serum and tissue samples from a large cohort of ECD patients focusing on two major pro-fibrotic mediators, TGF-β1 and chemokine ligand 18 (CCL18). We found a marked increase in CCL18 but not TGF-β1 levels in serum and lesions of ECD patients (), independently of treatment status and consistently over time. Using a linear mathematical model, we also found that elevated CCL18 serum levels correlate with both number and severity of disease localizations. These findings suggest the involvement of CCL18-induced fibrosis in ECD pathogenesis, providing a rationale for exploring CCL18 inhibition as a treatment for progressive fibrosis in ECD.
厄德里希-切斯特病（ECD）是一种罕见的组织细胞增多症，其特征是泡沫状组织细胞对黄瘤性肉芽肿组织的浸润。纤维化是ECD的组织学特征，是病变生长和临床表现的原因。阐明ECD中的分子纤维化途径将有助于识别新的药物靶点。在本研究中，我们评估了一大群ECD患者的血清和组织样本，重点关注两种主要的促纤维化介质，转化生长因子-β1（TGF-β1）和趋化因子配体18（CCL18）。我们发现，ECD患者血清和病变中的CCL18水平显著升高，而TGF-β1水平未升高（），与治疗状态无关且随时间持续存在。使用线性数学模型，我们还发现CCL18血清水平升高与疾病定位的数量和严重程度均相关。这些发现提示CCL18诱导的纤维化参与了ECD的发病机制，为探索抑制CCL18作为ECD进行性纤维化的治疗方法提供了理论依据。
