Clinical course of sarcoidosis in dependence on HLA-DRB1 allele frequencies, inflammatory markers, and the presence of M. tuberculosis DNA fragments

Sarcoidosis Vasc Diffuse Lung Dis. 2005 Mar;22(1):66-74.

Abstract

Background and aim: 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.

MeSH terms

  • Adult
  • Antigens, Bacterial
  • Biomarkers
  • Bronchoalveolar Lavage Fluid
  • DNA, Bacterial
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Frequency
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Humans
  • Inflammation*
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / pathogenicity
  • Polymerase Chain Reaction
  • Prognosis
  • Sarcoidosis / genetics*
  • Sarcoidosis / pathology*

Substances

  • Antigens, Bacterial
  • Biomarkers
  • DNA, Bacterial
  • HLA-DR Antigens
  • HLA-DRB1 Chains