Diagnosis of disease-specific proteins in cerebrospinal fluid of children infected with tuberculous meningitis

BACKGROUND： Isolated mycobacterium tuberculosis from cerebrospinal fluid （CSF） is regarded as the ＂gold standard＂ for diagnosis of tuberculous meningitis （TBM）. However, culture of CSF specimens is time-consuming and lacks sensitivity. There is a strong need to determine complementary disease-specific markers, which are essential for increasing early diagnosis and improving prognosis in patients with TBM OBJECTIVE： To establish proteomic profiles of CSF in TBM and normal children using two-dimensional polyacrylamide gel electrophoresis, and to screen for disease-specific proteins. DESIGN, TIME AND SETTING： The case-control study was conducted at the Department of Pediatrics, Xiangya Hospital of Central South University and the Key Laboratory of Cancer Proteomics of Ministry of Public Health of China between January 2008 and January 2009. PARTICIPANTS： The TBM group included three patients with a strongly positive tuberculin skin test, as well as positive CSF mycobacterial staining and culture, who were admitted to the Department of Pediatrics, Xiangya Hospital from January 2008 to January 2009. Three healthy, age- and gender-matched children served as the control group. METHODS： CSF proteins were separated using two-dimensional polyacrylamide gel electrophoresis in both groups. Gels were scanned using Image scanner and LabScan software. Differentially expressed proteins were analyzed using PDQuest 7.0 software. The clearly discernible spots, which were expressed only in the TBM group, were chosen to perform matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. MAIN OUTCOME MEASURES： Differentially expressed spots on CSF profiles of TBM and normal children were measured. RESULTS： Following comparison of two-dimensional polyacrylamide gel electrophoresis maps between TBM and control groups, 546 and 533 spots were detected, respectively. A total of 64 differentially expressed proteins were observed between the groups, including 15 upregulated spots, eight downregulated spots, 27 spots that were exclusively expressed in the TBM group, and 14 spots that were exclusively expressed in the control group. At total of 20 spots that were exclusively expressed in the TBM group were chosen for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, and 20 peptide mass fingerprints were obtained. After searching the data base, 16 proteins were matched. CONCLUSION： Two-dimensional polyacrylamide gel electrophoresis profiles of the CSF proteome were successfully established in the TBM and normal children. Parts of these differentially expressed proteins were identified through mass spectrometry and bioinformatics. Results indicated that apolipoprotein A I, anti-tumor necrosis factor-alpha antibody, crystal structure of MRP14 and HLA class II histocompatibility antigen DRB1-4 could be closely correlated with TBM pathogenesis.

Extra-Pulmonary Pott’s Disease with Intracranial Manifestations: An Inmate’s Story

Tuberculosis is a chronic disease that is the leading cause of infectious disease deaths worldwide. In developed countries, incidences are minimal and however, complicated manifestations of tuberculosis are becoming a trend within the prison system. This case report illustrates a patient within the United States correctional system who demonstrated a rare infection of tuberculosis despite absent pulmonary findings. Our Patient was a 39-year-old inmate presenting with fatigue, night sweats, weight loss, and progressive dyspnea. Pulmonary imaging and cultures of sputum were negative for tuberculosis. Further imaging and laboratory workups demonstrated extensive spinal infections along with intracranial lesions that were positive for tuberculosis. Neurosurgery declined operative medicine due to advancement of the disease and appropriate antibiotic therapy was immediately initiated. Tuberculosis continues to exist in developed countries with an increased emergence of complicated cases. Furthermore, incarceration dramatically increases an individual’s risk of worse infections. The clinical impact involves promoting awareness for a need to identify and prevent continued spread of disseminated infections. Therefore, further investigations of this trend in prisons are worth considering.