title: Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon gamma assay.
abstract: OBJECTIVE
  To analyse the performance of a new M. tuberculosis-specific interferon gamma (IFNgamma) assay in patients with chronic inflammatory diseases who receive immunosuppressive drugs, including tumour necrosis factor alpha (TNFalpha) inhibitors.
  
  
  METHODS
  Cellular immune responses to the M. tuberculosis-specific antigens ESAT-6, CFP-10, TB7.7 were prospectively studied in 142 consecutive patients treated for inflammatory rheumatic conditions. Results were compared with tuberculin skin tests (TSTs). Association of both tests with risk factors for latent M. tuberculosis infection (LTBI) and BCG vaccination were determined and the influence of TNFalpha inhibitors, corticosteroids, and disease modifying antirheumatic drugs (DMARDs) on antigen-specific and mitogen-induced IFNgamma secretion was analysed.
  
  
  RESULTS
  126/142 (89%) patients received immunosuppressive therapy. The IFNgamma assay was more closely associated with the presence of risk factors (odds ratio (OR) = 23.8 (95% CI 5.14 to 110) vs OR = 2.77 (1.22 to 6.27), respectively; p = 0.009), but less associated with BCG vaccination than the TST (OR = 0.47 (95% CI 0.15 to 1.47) vs OR = 2.44 (0.74 to (8.01), respectively; p = 0.025). Agreement between the IFNgamma assay and TST results was low (kappa = 0.17; 95% CI 0.02 to 0.32). The odds for a positive IFNgamma assay strongly increased with increasing prognostic relevance of LTBI risk factors. Neither corticosteroids nor conventional DMARDs significantly affected IFNgamma responses, but the odds for a positive IFNgamma assay were decreased in patients treated with TNFalpha inhibitors (OR = 0.21 (95% CI 0.07 to 0.63), respectively; p = 0.006).
  
  
  CONCLUSIONS
  These results demonstrate that the performance of the M. tuberculosis antigen-specific IFNgamma ELISA is better than the classic TST for detection of LTBI in patients receiving immunosuppressive therapy for treatment of systemic autoimmune disorders.
authors.affiliation: Department of Rheumatology and Clinical Immunology/Allergology, University of Bern, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Matulis
authors.forename: P
authors.initials: P
authors.lastname: Jüni
authors.forename: P M
authors.initials: PM
authors.lastname: Villiger
authors.forename: S D
authors.initials: SD
authors.lastname: Gadola
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology; D001500:BCG Vaccine; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D016867:Immunocompromised Host; D007159:Immunologic Tests; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D007371:Interferon-gamma / Q000097:blood; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016017:Odds Ratio; D011446:Prospective Studies; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D012307:Risk Factors; D014374:Tuberculin Test; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma; D000069285:Infliximab; D008727:Methotrexate