Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: Implications for pathogenesis

Antonella Stoppacciaro, Marina Ferrarini, Chiara Salmaggi, Cristina Colarossi, Luisa Praderio, Moreno Tresoldi, Angelo A. Beretta, Maria Grazia Sabbadini

Research output: Contribution to journalArticlepeer-review


Objective. Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis (LCH) of unknown etiology, characterized by diffuse histiocyte infiltration of bones and soft tissue. The purpose of this study was to assess cell proliferation and expression of cytokines, chemokines, and chemokine receptors that may potentially be important in histiocyte accumulation in ECD lesions. Methods. Biopsies were performed on 3 patients with ECD. The diagnosis of the disease was based on clinical signs including typical radiologic osteosclerosis, and on the detection of foamy CD68+,CD1a- non-Langerhans' cell histiocytes on histologic examination. The expression of the proliferation marker Ki-67 as well as of selected chemokine/cfaemokine receptor pairs and cytokines was analyzed by immunohistochemistry. Results. In all samples, Ki-67 was undetectable in CD68+ histiocytes. Conversely, these cells expressed the chemokines CCL2 (monocyte chemotactic protein 1), CCL4/macrophage inflammatory protein 1β (MIP-1β), CCL5/RANTES, CCL20/MIP-3α, and CCL19/MIP-3β, and their counter-receptors CCR1, CCR2, CCR3, CCR5, CCR6, and CCR7. Moreover, ECD histiocytes expressed inierferon-γ-inducible 10-kd protein (CXCL10), which is specifically induced by interferon-γ, and interleukin-6 and RANKL, which are both implicated cated in bone remodeling. Finally, all cases showed a Th1-type lymphocyte infiltrate. Conclusion. Our data indicate that, similar to LCH, ECD lesions are characterized by a complex cytokine and chemokine network, which may orchestrate histiocyte activation and accumulation through an autocrine loop and contribute to the pathogenesis of the disease.

Original languageEnglish
Pages (from-to)4018-4022
Number of pages5
JournalArthritis and Rheumatism
Issue number12
Publication statusPublished - Dec 2006

ASJC Scopus subject areas

  • Immunology
  • Rheumatology


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