title: Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles.
abstract: OBJECTIVE
  To evaluate peripheral blood T-helper (TH) cell-associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters.
  
  
  METHODS
  A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS.
  
  
  RESULTS
  Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS subjects compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α, and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody.
  
  
  CONCLUSIONS
  This is the first time that multiple cytokines and chemokines have been examined simultaneously in LS. In general, a TH1 (IFN-γ) and TH17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN-γ signature with elevated IP-10, MCP-1, and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α, and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting.
authors.affiliation: Division of Pediatric Rheumatology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224; Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA. Electronic address: kathryn.torok@chp.edu.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Torok
authors.affiliation: Division of Pediatric Rheumatology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kurzinski
authors.affiliation: Division of Pediatric Rheumatology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224.
authors.forename: Christina
authors.initials: C
authors.lastname: Kelsey
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yabes
authors.affiliation: Division of Pediatric Rheumatology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Magee
authors.affiliation: Division of Pediatric Rheumatology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224; Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Abbe N
authors.initials: AN
authors.lastname: Vallejo
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Medsger
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA; Department of Medicine, Medical University of South Carolina, Charleston, SC.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Feghali-Bostwick
mesh_terms: D000293:Adolescent; D000077214:Becaplermin; D018932:Chemokine CCL2 / Q000097:blood; D018925:Chemokines / Q000097:blood*; D002648:Child; D016207:Cytokines / Q000097:blood*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D008297:Male; D020574:Proto-Oncogene Proteins c-sis / Q000097:blood; D018121:Receptors, Cytokine / Q000097:blood; D012594:Scleroderma, Localized / Q000097:blood*; D006377:T-Lymphocytes, Helper-Inducer
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; C104577:IP10-Mig receptor; D016898:Interferon-alpha; D020381:Interleukin-17; D020574:Proto-Oncogene Proteins c-sis; D018121:Receptors, Cytokine; D018664:Interleukin-12; D000077214:Becaplermin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Cytokines; Disease activity; Localized scleroderma; Luminex; Pediatric rheumatology; T-helper cells