Gene expression profiling of tuberculous meningitis

Tuberculous meningitis (TBM) is a form of extra pulmonary tuberculosis that is associated with severe neurological deficits and a high mortality. Early diagnosis of TBM is a major challenge despite the availability of several diagnostic methods. Existing diagnostic methods and markers are inadequate for early diagnosis of TBM owing to poor specificity and sensitivity. DNA microarray technology permits high-throughput identification of differentially expressed genes. In order to identify molecules as candidate biomarkers for early diagnosis or as therapeutic targets in TBM, we carried out transcriptomic analysis of brain tissue using whole human genome oligonucleotide arrays. From this gene expression analysis, we identified 2,434 genes that were differentially expressed at least two-fold in TBM cases as compared to controls. The large majority of the differentially expressed genes encoded proteins that are involved in metabolism, cell growth, transport, immune response, cell communication and signal transduction. We confirmed the upregulation of two molecules, serpin peptidase inhibitor, clade A member 3 (SERPINA3) and glial fibrillary acidic protein (GFAP), at the protein level by immunohistochemical analysis. The findings from our study should help us understand the molecular mechanisms underlying TBM and to develop better diagnostic and therapeutic strategies against this deadly disease.