Blood and site of disease inflammatory profiles differ in HIV-1-infected pericardial tuberculosis patients

ObjectivesTo better understand the pathogenesis of pericardial tuberculosis (PCTB), we sought to characterize the systemic inflammatory profile in HIV-1-infected participants with latent TB infection (LTBI), pulmonary TB (PTB) and PCTB. MethodsUsing Luminex, we measured 39 analytes in pericardial fluid (PCF) and paired plasma from 18 PCTB participants, and plasma from 16 LTBI and 20 PTB. Follow-up plasma samples were also obtained from PTB and PCTB participants. HLA-DR expression on Mtb-specific CD4 T cells was measured in baseline samples using flow cytometry. ResultsAssessment of the overall systemic inflammatory profile by principal component analysis showed that the inflammatory profile of active TB participants was distinct from the LTBI group, while PTB patients could not be distinguished from those with PCTB. In the LTBI group, 12 analytes showed a positive association with plasma HIV-1 viral load, and most of these associations were lost in the diseased groups. When comparing the inflammatory profile between PCF and paired blood, we found that the concentrations of most analytes (24/39) were elevated at site of disease. However, the inflammatory profile in PCF partially mirrored inflammatory events in the blood. After TB treatment completion, the overall plasma inflammatory profile reverted to those observed in the LTBI group. Lastly, HLA-DR expression showed the best performance for TB diagnosis compared to previously described biosignatures built from soluble markers. ConclusionOur results describe the inflammatory profile associated with PTB and PCTB and emphasize the potential role of HLA-DR as a promising biomarker for TB diagnosis.