Clinical course of sarcoidosis in dependence on HLA-DRB1 allele frequencies, inflammatory markers, and the presence of M. tuberculosis DNA fragments.
OBJECTIVE
For sarcoidosis it is generally hypothesized that inherited factors and environmental antigens may contribute to pathogenesis. Since M. tuberculosis DNA was found in a significant percentage of sarcoidosis patients, we analyzed the relationship between HLA-DRB1 alleles, inflammatory markers and the presence of M. tuberculosis DNA in sarcoidosis and its influence on clinical course.


METHODS
From 144 patients with sarcoidosis lung tissue, BAL and/or blood were investigated by means of PCR assays to detect an 123 bp multicopy element of M. tuberculosis DNA and HLA-DRB1 alleles, respectively. ACE was measured spectrophotometrically, sIL-2R by ELISA. Clinical data describing the disease course were available from 63 patients.


RESULTS
The percentage of M. tuberculosis positive sarcoidosis patients was significantly increased in the chronic patients group compared to acute disease. The percentage of HLA-DRB 1*03 positive patients was significantly higher in acute sarcoidosis, whereas in chronic disease the HLA-DRB1*11 positive patients were clearly over-represented. In addition, we found a highly significant correlation of HLA-DRB1*11 or -DRB1*15 alleles and/or the presence of M. tuberculosis DNA to a chronic disease course, whereas HLA-DRB1*03 or -DRB1*04 alleles combined with the absence of M. tuberculosis DNA were associated with an acute sarcoidosis (p = 0.009). ACE and sIL2-R serum levels were significantly higher in M. tuberculosis positive sarcoidosis independent of the HLA-DRB1 specificity, but did not differ between acute and chronic disease course alone.


CONCLUSIONS
The association between certain HLA-DR antigens, the presence of M. tuberculosis DNA and disease course indicates that specific antigens of M. tuberculosis may play a pathogenetic role in chronic sarcoidosis.
Grosser
Marianne
M
Institut für Pathologie, Technische Universität Dresden, D-01307 Dresden, Germany.
Luther
Thomas
T
Fuessel
Monika
M
Bickhardt
Jakob
J
Magdolen
Viktor
V
Baretton
Gustavo
G
D000328:Adult; D000942:Antigens, Bacterial; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid; D004269:DNA, Bacterial; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012507:Sarcoidosis / Q000235:genetics* / Q000473:pathology*
D000942:Antigens, Bacterial; D015415:Biomarkers; D004269:DNA, Bacterial; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains