Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: implications for pathogenesis.
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.
Stoppacciaro
Antonella
A
University of Rome La Sapienza, Rome, Italy.
Ferrarini
Marina
M
Salmaggi
Chiara
C
Colarossi
Cristina
C
Praderio
Luisa
L
Tresoldi
Moreno
M
Beretta
Angelo A
AA
Sabbadini
Maria Grazia
MG
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
D015415:Biomarkers; D018925:Chemokines; D005938:Glucocorticoids; D019394:Ki-67 Antigen; D019386:Alendronate