In active tuberculosis (TB), Mycobacterium tuberculosis-specific T cells are compartmentalized more to the site of infection than to the circulating blood. Therefore, an M. tuberculosis-specific enzyme-linked immunospot (ELISPOT) assay with samples from the site of infection may permit a more sensitive or specific diagnosis of active central nervous system (CNS) TB than that achieved by the assay with blood alone. Therefore, we prospectively evaluated the usefulness of circulating and compartmentalized mononuclear cell (MC; i. and 25 (68%) were classified as not having active TB. The sensitivity and specificity of the PBMC ELISPOT assay were 91% (95% confidence interval [CI], 59% to 100%) and 63% (95% CI, 41% to 81%), respectively. By comparison, the sensitivity and specificity of the CSF MC ELISPOT assay were 75% (95% CI, 19% to 99%) and 75% (95% CI, 43% to 95%), respectively. When the ratio of the CSF MC ELISPOT assay results to the PBMC ELISPOT results was 2 or more, the sensitivity and specificity were 50% (95% CI, 7% to 93%) and 100% (95% CI, 74% to 100%), respectively. The ELISPOT assay with PBMCs and CSF MCs is a useful adjunct to the current tests for the diagnosis of CNS TB.The diagnosis of central nervous system (CNS) tuberculosis (TB) remains a serious clinical problem (1). The signs and symptoms, the results of routine analyses of cerebrospinal fluid (CSF), and the radiologic findings for patients with CNS TB are often inadequate as a guide to the initiation of empirical therapy (1). Therefore, a rapid, sensitive, and specific test for the diagnosis of CNS TB is urgently required. Several newly developed assays for the diagnosis of TB based on Mycobacterium tuberculosis-specific antigens encoded by genes in the RD1 region gave promising results for the detection of latent TB infection and active pulmonary TB (10). However, data on the usefulness of these assays for the diagnosis of CNS TB in actual clinical practice are limited.The clinical use of the immunodiagnosis of TB is limited in regions where TB has intermediate to high levels of endemicity because it cannot differentiate active TB from latent TB infection (6). Recently, it has been shown that mononuclear cells (MCs) compartmentalized in infected sites such as pleural fluid (8,14) or bronchoalveolar lavage fluid (3, 5) have higher gamma interferon responses than peripheral blood mononuclear cells (PBMCs). We aimed to demonstrate the proof of concept for the ability of the enzyme-linked immunospot (ELISPOT) assay to differentiate active TB from latent TB using compartmentalized lymphocytes. Therefore, we prospectively evaluated the usefulness of circulating and compartmentalized MC-based ELISPOT assays for the diagnosis of active TB in patients with suspected CNS TB.
MATERIALS AND METHODSAll adult patients with suspected CNS TB were prospectively enrolled at the Seoul National University Hospital, Seoul, Republic of Korea, and the Seoul National University Bundang Hospital in Gyunggi Province, Republic of Korea, between September 2006 and Augu...