Eotaxin/CCL11 in idiopathic retroperitoneal fibrosis

Autor: Matteo Goldoni, Maria Luisa Carnevali, Domenico Corradi, Paolo Govoni, Carlo Buzio, Veronica Bartoli, Irene Libri, Alessandra Palmisano, Domenica Mangieri, Rossella Alinovi, Augusto Vaglio, Davide Martorana, Giovanni Malerba
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Eotaxin
Chemokine CCL11
Male
Pathology
medicine.medical_specialty
Receptors
CCR3
Becaplermin
Tryptase
chemokines
chemokines
eosinophils
eotaxin/CCL11
haplotype analysis
idiopathic retroperitoneal fibrosis
Polymorphism
Single Nucleotide
Fibrosis
idiopathic retroperitoneal fibrosis
Granulocyte Colony-Stimulating Factor
medicine
Eosinophilia
Humans
Mast Cells
Immunogenetic Phenomena
Idiopathic Retroperitoneal Fibrosis
Chemokine CCL5
CCL11
Genetic Association Studies
Transplantation
biology
business.industry
Interleukin
Retroperitoneal Fibrosis
Proto-Oncogene Proteins c-sis
respiratory system
Eosinophil
Middle Aged
medicine.disease
medicine.anatomical_structure
Haplotypes
Nephrology
Case-Control Studies
haplotype analysis
Immunology
eotaxin/CCL11
biology.protein
Female
Fibroblast Growth Factor 2
eosinophils
medicine.symptom
Interleukin-5
business
Popis: Background. Idiopathic retroperitoneal fibrosis (IRF) is a rare fibro-inflammatory disorder characterized by a periaortic tissue which often encases the ureters causing acute renal failure. IRF histology shows fibrosis and a chronic inflammatory infiltrate with frequent tissue eosinophilia. We assessed a panel of molecules promoting eosinophilia and fibrosis in IRF patients and performed an immunogenetic study. Methods. Serum levels of eotaxin/CCL11, regulated and normal T-cell expressed and secreted (RANTES), granulocyte colony-stimulating factor (G-CSF), interleukin (IL)5, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) were measured using a multiplex assay in 24 newly diagnosed, untreated IRF patients and 14 healthy controls. Retroperitoneal biopsies (available in 8/24 patients) were histologically evaluated to assess eosinophil infiltration, whereas mast cells (MCs) were identified by immunohistochemical analysis for human tryptase. Immunohistochemistry for eotaxin/CCL11 and its receptor CCR3 was also performed. Six single nucleotide polymorphisms (SNPs) within the CCL11 gene (rs6505403, rs1860184, rs4795896, rs17735961, rs16969415 and rs17809012) were investigated in 142 IRF patients and 214 healthy controls. Results. Serum levels of eotaxin/CCL11 were higher in IRF patients than in controls (P = 0.009). Eotaxin/CCL11 drives tissue infiltration of eosinophils and MCs, which can promote fibrosis. Eosinophilic infiltration was prominent (>5 cells/hpf) in five (62.5%) cases, and abundant tryptase-positive MCs were found in all cases; notably, MCs were in a degranulating state. Immunohistochemistry showed that CCL11 was highly produced by infiltrating mononuclear cells and that its receptor CCR3 was expressed by infiltrating eosinophils, MCs, lymphocytes and fibroblasts. None of the tested CCL11 SNPs showed disease association, but the TTCCAT haplotype was significantly associated with IRF (P = 0.0005). Conclusions. These findings suggest that the eotaxin/ CCL11-CCR3 axis is active in IRF and may contribute to its pathogenesis; the TTCCAT haplotype within the CCL11 gene is significantly associated with IRF.
Databáze: OpenAIRE
Externí odkaz: