The Fibrogenic Chemokine CCL18 is Associated with Disease Severity in Erdheim-Chester Disease

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2018 Jun 15

PMID 29900045

Citations 10

Authors

Greta Pacini

Giulio Cavalli

Alessandro Tomelleri

Giacomo De Luca

Guido Pacini

Marina Ferrarini

Claudio Doglioni

Lorenzo Dagna

Affiliations

Soon will be listed here.

Abstract

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.

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