Abstract
Immunocompromised patients with acid-fast bacilli (AFB) smear-negative active pulmonary tuberculosis (pTB) often present with nonspecific clinical symptoms and findings. T-cell interferon-gamma release assays (TIGRA) performed on whole blood (using ELISA) or peripheral blood mononuclear cells (using enzyme-linked immunospot assay (ELISPOT)) are more sensitive for the diagnosis of Mycobacterium tuberculosis (MTB) infection than the tuberculin skin test (TST), but cannot distinguish active from latent MTB infection. The present authors report a 38-yr-old female presenting with a 3-week history of malaise, dyspnoea, fevers and coughing, who had received immunosuppressive therapies over 8 months for mixed connective tissue disease. Chest radiograph and thoracic computed tomography showed ground glass opacities in both lower lobes. The TST-induration was 0 mm and AFBs or MTB nucleic acid was not detected on sputum and bronchial secretions. However, TIGRAs performed on peripheral blood cells were reactive. A high frequency of MTB-specific T-cells compatible with the immunodiagnosis of active pTB was detected among bronchoalveolar lavage cells using ELISPOT. Antituberculous therapy was initiated 18 days before MTB was discovered on sputum cultures. Detection of Mycobacterium tuberculosis-specific T-cells in the bronchoalveolar lavage using enzyme-linked immunospot assay is a promising tool for the diagnosis of active pulmonary tuberculosis in immunocompromised patients with negative acid-fast bacilli smears.
Highlights
The present authors report a 38-yr-old female presenting with a 3-week history of malaise, dyspnoea, fevers and coughing, who had received immunosuppressive therapies over 8 months for mixed connective tissue disease
Detection of Mycobacterium tuberculosis-specific T-cells in the bronchoalveolar lavage using enzyme-linked immunospot assay is a promising tool for the diagnosis of active pulmonary tuberculosis in immunocompromised patients with negative acid-fast bacilli smears
When detection of acid-fast bacilli (AFB) in sputum or bronchial secretions is not possible and Mycobacterium tuberculosis (MTB) DNA cannot be detected by nucleic acid amplification, the diagnosis of pulmonary tuberculosis (pTB) by identification of MTB in liquid or solid culture media is delayed for several weeks [5]
Summary
The diagnosis of mixed connective tissue disease (MCTD) was performed and treatment with prednisolone at a dosage of 20 mg was reinitiated without continuing methotrexate Despite these interventions, the patient suffered from ongoing fever up to 39uC. Tuberculin PPD RT 23 SSI (2 TU/0.1 mL solution for injection; Statens Serum Institute, Copenhagen, Denmark) revealed 0 mm of induration after 48 and 72 h With another MTBspecific TIGRA, the T-SPOT.TB assay (Oxford Immunotec, Abingdon, UK), 59 and 31 spot-forming cells (SFCs) per 250,000 peripheral blood mononuclear cells (PBMCs) were enumerated in response to ESAT-6 and CFP-10 in blood samples MTB-specific ELISPOT (Oxford Immunotec) was performed on BAL mononuclear cells (BALMCs) as previously described [7], to discriminate active TB from LTBI. Net numbers of spot-forming cells (SFCs) and interpretation of Mycobacterium tuberculosisspecific enzyme-linked immunospot assay reactivity
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