title: Association between increased CCL2 (MCP-1) expression in lesions and persistence of disease activity in giant-cell arteritis.
abstract: OBJECTIVE
  Patients with giant-cell arteritis (GCA) usually respond dramatically to corticosteroid treatment. However, recurrences are frequent and corticosteroid requirements are highly variable among patients. The aim of our study was to identify genes potentially involved in disease persistence.
  
  
  METHODS
  Gene expression was explored with cDNA arrays in temporal artery biopsies from six GCA patients with relapsing disease and six patients who easily achieved sustained remission. Differentially expressed genes of interest were subsequently analysed by quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry in temporal artery biopsies from 35 patients with biopsy-proven GCA and nine controls.
  
  
  RESULTS
  CCL2 (MCP-1) was up-regulated in temporal artery samples from relapsing individuals. In the extended series of patients, CCL2 mRNA concentration in lesions was significantly higher than in controls (31 +/- 15.6 vs 0.44 +/- 0.10, P = 0.0001). In addition, CCL2 was more abundant in patients who experienced two or more relapses during the first year compared with those who endured sustained remission (127 +/- 82 vs 11 +/- 5.5, P = 0.0233) and correlated with the cumulated prednisolone dose (R = 0.533, P = 0.0024). CCL2 mRNA concentration correlated with IL-1beta (R = 0.45, P = 0.02), tumour necrosis factor-alpha (TNF-alpha) (R = 0.47, P = 0.013) and IL-6 (R = 0.52, P = 0.0053) mRNA. However, circulating CCL2 determined by ELISA was decreased in patients with strong systemic inflammatory response, suggesting that reduction in circulating CCL2 may reinforce the local gradient in lesions.
  
  
  CONCLUSIONS
  Increased CCL2 (MCP-1) expression in lesions is associated with persistence of disease activity in GCA.
authors.affiliation: Department of Internal Medicine, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain. mccid@clinic.ub.es
authors.forename: M C
authors.initials: MC
authors.lastname: Cid
authors.forename: M P
authors.initials: MP
authors.lastname: Hoffman
authors.forename: J
authors.initials: J
authors.lastname: Hernández-Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Segarra
authors.forename: M
authors.initials: M
authors.lastname: Elkin
authors.forename: M
authors.initials: M
authors.lastname: Sánchez
authors.forename: C
authors.initials: C
authors.lastname: Vilardell
authors.forename: A
authors.initials: A
authors.lastname: García-Martínez
authors.forename: M
authors.initials: M
authors.lastname: Pla-Campo
authors.forename: J M
authors.initials: JM
authors.lastname: Grau
authors.forename: H K
authors.initials: HK
authors.lastname: Kleinman
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D013700:Giant Cell Arteritis / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D011239:Prednisolone / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism; D012008:Recurrence; D013699:Temporal Arteries / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D018076:DNA, Complementary; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D011239:Prednisolone