title: Linkage of type I interferon activity and TNF-alpha levels in serum with sarcoidosis manifestations and ancestry.
abstract: BACKGROUND
  Both type I interferon (IFN), also known as IFN-α and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes.
  
  
  METHODS
  We studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-α was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman's rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations.
  
  
  RESULTS
  Significant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-α levels were significantly higher relative to matched controls (P = 0.039), and patients with neurologic disease had significantly higher TNF-α than patients lacking this manifestation (P = 0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P = 0.0032). None of the associations observed were shared between the two ancestral groups.
  
  
  CONCLUSIONS
  Our data indicate that significant associations between serum levels of TNF-α and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease.
authors.affiliation: Section of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America. nsweiss@uic.edu
authors.forename: Nadera J
authors.initials: NJ
authors.lastname: Sweiss
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Franek
authors.forename: Silvia N
authors.initials: SN
authors.lastname: Kariuki
authors.forename: David R
authors.initials: DR
authors.lastname: Moller
authors.forename: Karen C
authors.initials: KC
authors.lastname: Patterson
authors.forename: Peggy
authors.initials: P
authors.lastname: Bennett
authors.forename: Lakshmi R
authors.initials: LR
authors.lastname: Girijala
authors.forename: Vaisak
authors.initials: V
authors.lastname: Nair
authors.forename: Robert P
authors.initials: RP
authors.lastname: Baughman
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005789:Genealogy and Heraldry; D006801:Humans; D007370:Interferon Type I / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D012507:Sarcoidosis / Q000097:blood* / Q000145:classification; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D044465:White People; D055815:Young Adult
chemical_list: D007370:Interferon Type I; D014409:Tumor Necrosis Factor-alpha