title: Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.
abstract: BACKGROUND
  Sarcoidosis is a systemic disorder of unknown cause, highly variable phenotype and unpredictable outcome. Antigen processing, inflammatory response and immunomodulation appear critical to development and prognosis of the disease.
  
  
  METHODS
  We performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HUG95A, Affymetrix Inc.) for gene expression profiling from peripheral blood of patients with acute pulmonary sarcoidosis (n = 12) and matched healthy controls (n = 12), mean age 36 +/- 12 and 33 +/- 10 years respectively.
  
  
  RESULTS
  At follow-up (18 [15-24] months), 7 patients had self-limited disease and 5 had persistent disease. Significantly different expression comparing patients and controls was identified for 1,860 (14.9%) and 729 (5.8%) gene products at p = 0.05 and p = 0.01 levels respectively. Genes closely associated with persistent disease included HLA-DRB1*1501 DQB1*0602, TNFA, NFKB, cyclic AMP-responsive element modulator (CREM) and T-cell activation marker CD69. IL1B, IL8, growth related (GRO)-beta/-gamma and CCR 2,5,6 were closely associated with self-limited disease.
  
  
  CONCLUSIONS
  We hypothesize that, in self-limited disease, greater effector cell activation leads to successful antigen elimination/tolerance, whereas HLA-DRB1*1501 DQBI*0602-mediated, probably defective/partial T-lymphocyte activation results in an inefficient primary immune response, antigen intolerance and persistent disease.
authors.affiliation: Department of Respiratory Medicine, University Hospital, Galway, Ireland.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rutherford
authors.forename: Frank
authors.initials: F
authors.lastname: Staedtler
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kehren
authors.forename: Salah-Dine
authors.initials: SD
authors.lastname: Chibout
authors.forename: Ladina
authors.initials: L
authors.lastname: Joos
authors.forename: Michel
authors.initials: M
authors.lastname: Tamm
authors.forename: John J
authors.initials: JJ
authors.lastname: Gilmartin
authors.forename: Martin H
authors.initials: MH
authors.lastname: Brutsche
mesh_terms: D000328:Adult; D017951:Antigen Presentation / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D017565:Sarcoidosis, Pulmonary / Q000235:genetics* / Q000276:immunology* / Q000473:pathology