Blood transcriptional signature of HIV-associated tuberculous meningitis

Patients with HIV-associated TB meningitis (TBM) are known to experience systemic hyperinflammation, clinically known as immune reconstitution inflammatory syndrome (IRIS), following the commencement of antiretroviral therapy (ART). No prognostic markers or biomarkers have been identified to date and little is known about the mechanism mediating the hyperinflammation. We recruited a prospective cohort of 33 patients with HIV-associated TBM, 16 of whom developed TBM-IRIS, and performed transcriptomic profiling. Transcriptomic signatures that distinguish patients who would eventually develop IRIS were identified and indicated neutrophil and inflammasome activation as being the predominant mediator of TBM-IRIS pathogenesis. Patients are classified either as TBM-IRIS and non-IRIS and longitudinal samples (TBM-diagnosis, 2wpTBRx and 2wpART) were anlayzed. A control group of 17 patients HIV-1 infected patients without TBM and not on ART were also included. There are a total of 116 samples (33 TBM at 3 timepoints and 17 control at 1 timepoint). For noramlization, all samples were baseline transformed to the median of all samples.