Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.
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.
Rutherford
Robert M
RM
Department of Respiratory Medicine, University Hospital, Galway, Ireland.
Staedtler
Frank
F
Kehren
Jeanne
J
Chibout
Salah-Dine
SD
Joos
Ladina
L
Tamm
Michel
M
Gilmartin
John J
JJ
Brutsche
Martin H
MH
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