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Clinical and Vaccine Immunology, September 2008, p. 1356-1362, Vol. 15, No. 9
1071-412X/08/$08.00+0     doi:10.1128/CVI.00040-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Diagnosis of Central Nervous System Tuberculosis by T-Cell-Based Assays on Peripheral Blood and Cerebrospinal Fluid Mononuclear Cells{triangledown}

Sung-Han Kim,1,3 Kon Chu,2 Su-Jin Choi,3 Kyoung-Ho Song,1 Hong-Bin Kim,1 Nam-Joong Kim,1 Seong-Ho Park,2 Byung-Woo Yoon,2 Myoung-don Oh,1,3* and Kang-Won Choe1,3

Departments of Internal Medicine,1 Neurology, Seoul National University College of Medicine,2 Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea3

Received 25 January 2008/ Returned for modification 11 May 2008/ Accepted 2 July 2008

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.e., peripheral blood mononuclear cell [PBMC] and cerebrospinal fluid [CSF] MC)-based ELISPOT assays (i.e., the T-SPOT.TB test) for the diagnosis of active TB in patients with suspected CNS TB. The clinical categories of CNS TB were classified as described previously (G. E. Thwaites, T. T. Chau, K. Stepniewska, N. H. Phu, L. V. Chuong, D. X. Sinh, N. J. White, C. M. Parry, and J. J. Farrar, Lancet 360:1287-1292, 2002). Thirty-seven patients with suspected CNS TB were enrolled over a 12-month period. Of these, 31 (84%) showed clinical manifestations of suspected TB meningitis and 6 (16%) gave indications of intracranial tuberculoma with disseminated TB. The final clinical categories of the 37 patients with suspected CNS TB were as follows: 12 (32%) were classified as having CNS TB (7 with confirmed TB, 3 with probable TB, and 2 with possible TB) 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.


* Corresponding author. Mailing address: Department of Internal Medicine, Seoul National University Hospital, 28 Youngun-dong, Chongro-gu, Seoul 110-744, Republic of Korea. Phone: 82-2-2072-2945. Fax: 82-2-762-9662. E-mail: mdohmd{at}snu.ac.kr

{triangledown} Published ahead of print on 16 July 2008.


Clinical and Vaccine Immunology, September 2008, p. 1356-1362, Vol. 15, No. 9
1071-412X/08/$08.00+0     doi:10.1128/CVI.00040-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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