title: Beryllium-specific CD4+ T cells in blood as a biomarker of disease progression.
abstract: BACKGROUND
  CD4(+) T cells are responsible for the progressive lung damage seen in patients with chronic beryllium disease (CBD), a granulomatous lung disorder in which antigen-specific, T(H)1-type, cytokine-secreting T cells have been characterized. Compared with those seen in beryllium (Be)-sensitized subjects, increased numbers of Be-responsive T cells are present in the blood of patients with CBD.
  
  
  OBJECTIVE
  The aim of this study was to determine whether the number of Be-specific T cells in blood predicted the development of CBD in a cohort of Be-exposed subjects.
  
  
  METHODS
  Using IFN-γ ELISpot and proliferation-based assays, we determined the frequency and proliferative capacity of Be-responsive T cells in blood.
  
  
  RESULTS
  Compared with the Be lymphocyte proliferation test, which detected an abnormal Be-induced proliferative response in 11 (4.2%) of 260 workers from a Be-machining facility, the IFN-γ ELISpot detected a sensitization rate of 10% (χ(2) = 55.7, P < .0001). A significant positive correlation was also noted between the number of Be-responsive CD4(+) T cells in the blood and lung tissue of patients with CBD. Importantly, the transition from Be sensitization to CBD was associated with an increased number of antigen-specific T cells in blood.
  
  
  CONCLUSIONS
  These findings have important implications for Be-induced disease and potentially other immune-mediated disorders, suggesting that the frequency of antigen-specific T cells in blood can serve as a noninvasive biomarker to predict disease development and severity of the Be-specific CD4(+) T-cell alveolitis.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colo 80045, USA.
authors.forename: Allison K
authors.initials: AK
authors.lastname: Martin
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mack
authors.forename: Michael T
authors.initials: MT
authors.lastname: Falta
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Mroz
authors.forename: Lee S
authors.initials: LS
authors.lastname: Newman
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fontenot
mesh_terms: D000328:Adult; D000368:Aged; D001607:Berylliosis / Q000097:blood* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers