Tuberculous Meningitis in Patients Without Systemic Focus of Miliary Tuberculosis

Antigen 85 (Ag 85) complex, a component of M.tuberculosis bacilli (MTB) have been the focus of extensive research for diagnosis of tuberculosis for last several years. The aim of the present study to evaluate the status of primary tuberculosis infection in confirmed tuberculous meningitis (TBM) patients by estimating Ag 85 complex in Cerebrospinal Fluid (CSF) and serum specimen. A prospective study was also conducted to evaluate response of B cells derived from the CSF and serum of TBM patients after challenging with the Ag 85 complex. CSF and blood samples with and without heparin were collected from all the study subjects. An indirect ELISA was performed using monoclonal antibody (mAb) against Ag 85 complex for the demonstration of Ag 85 complex antigen in CSF and serum specimen of TBM patients. Cell ELISA was also done to evaluate the response of B cells derived from CSF and serum of TBM patients against Ag 85 complex. The CSF positivity for Ag 85 complex in TBM patients was 100% (35/35) however serum of same patients was positive for only 9% (3/35) cases. B cell response against Ag 85 complex was observed only in cells isolated from CSF rather than blood cells. Ag 85 complex activity and B cell response was found to be negative for control group (within 72 h). The absence of Ag 85 complex activity and B cell response in blood sample suggest a systemic focus of tuberculosis is possibly absent in blood and B-cell response lacking systemic feedback control. Ag 85 complex turn out to be an important molecular marker to understand the immune response in TBM patients associated with localized humoral response in central nervous system.