title: High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis.
abstract: OBJECTIVE
  Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18, which has been linked to pulmonary inflammation, is an interesting candidate, but data have not been consistent. We aimed to assess CCL18 levels in a large, prospective, unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis.
  
  
  METHODS
  Sera from the Oslo University Hospital SSc cohort (n = 298) and healthy control subjects (n = 100) were analyzed for CCL18 by enzyme immunoassay. High CCL18 (>53 ng/mL) was defined using the mean value plus 2 SD in sera obtained from healthy control subjects as the cutoff.
  
  
  RESULTS
  High serum CCL18 was identified in 35% (105 of 298). Annual decline in FVC differed significantly between high and low CCL18 subsets (13.3% and 4.7%; P = .016), as did the annual progression rate of lung fibrosis (0.9% [SD, 2.9] and 0.2% [SD, 1.9]). Highest rates of annual FVC decline > 10% (21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (< 3 years). In multivariate analyses, CCL18 was associated with annual FVC decline > 10% (OR, 1.1; 95% CI, 1.01-1.11) and FVC < 70% at follow-up (OR, 3.1; 95% CI, 1.08-8.83). Survival analyses showed that patients with high CCL18 had reduced 5- and 10-year cumulative survival compared with patients with low CCL18 (85% and 74%, compared with 97% and 89%, respectively; P = .001).
  
  
  CONCLUSIONS
  The results from this prospective cohort reinforce the notion that high CCL18 may serve as a marker for early identification of progressive ILD in SSc.
authors.affiliation: Department of Rheumatology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: a.m.hoffmann-vold@medisin.uio.no.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Hoffmann-Vold
authors.affiliation: Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
authors.forename: Anders Heiervang
authors.initials: AH
authors.lastname: Tennøe
authors.affiliation: Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
authors.forename: Torhild
authors.initials: T
authors.lastname: Garen
authors.affiliation: Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Midtvedt
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Aurelija
authors.initials: A
authors.lastname: Abraityte
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Trond Mogens
authors.initials: TM
authors.lastname: Aaløkken
authors.affiliation: Department of Respiratory Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: May Britt
authors.initials: MB
authors.lastname: Lund
authors.affiliation: Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Brunborg
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Department of Rheumatology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Molberg
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009664:Norway; D011379:Prognosis; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate; D014797:Vital Capacity
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC
keywords: cytokines; interstitial lung disease; scleroderma