title: Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: implications for pathogenesis.
abstract: 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/chemokine 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 1beta (MIP-1beta), CCL5/RANTES, CCL20/MIP-3alpha, and CCL19/MIP-3beta, and their counter-receptors CCR1, CCR2, CCR3, CCR5, CCR6, and CCR7. Moreover, ECD histiocytes expressed interferon-gamma-inducible 10-kd protein (CXCL10), which is specifically induced by interferon-gamma, and interleukin-6 and RANKL, which are both implicated in bone remodeling. Finally, all cases showed a Th1-type lymphocyte infiltrate.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Rome La Sapienza, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Stoppacciaro
authors.forename: Marina
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Chiara
authors.initials: C
authors.lastname: Salmaggi
authors.forename: Cristina
authors.initials: C
authors.lastname: Colarossi
authors.forename: Luisa
authors.initials: L
authors.lastname: Praderio
authors.forename: Moreno
authors.initials: M
authors.lastname: Tresoldi
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Beretta
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sabbadini
mesh_terms: D019386:Alendronate / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism*; D031249:Erdheim-Chester Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005269:Femur / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D005938:Glucocorticoids / Q000627:therapeutic use; D006644:Histiocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods*; D019394:Ki-67 Antigen / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D018925:Chemokines; D005938:Glucocorticoids; D019394:Ki-67 Antigen; D019386:Alendronate