Cytokine and chemokine expression profiles in response to Mycobacterium tuberculosis stimulation are altered in HIV-infected compared to HIV-uninfected subjects with active tuberculosis

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 95; no. 5; pp. 555 - 561
• Main Authors: Waruk, Jillian L.M., Machuki, Zipporah, Mesa, Christine, Juno, Jennifer A., Anzala, Omu, Sharma, Meenu, Ball, T. Blake, Oyugi, Julius, Kiazyk, Sandra
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.09.2015
• Subjects: Adult; Area Under Curve; Biomarkers - blood; Chemokine; Chemokines - blood; Co-infection; Coinfection; Cytokine; Cytokines - blood; Female; HIV; HIV Infections - blood; HIV Infections - diagnosis; HIV Infections - immunology; HIV Infections - virology; Host-Pathogen Interactions; Humans; Infectious Disease; Interferon gamma release assay; Interferon-gamma - blood; Interferon-gamma Release Tests; Kenya; Male; Middle Aged; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - pathogenicity; Predictive Value of Tests; Pulmonary/Respiratory; ROC Curve; ROC curve analysis; Tuberculosis; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; Kenya; ROC curve analysis; Cytokine; Treg; LTBI; ATB; IGRA; Chemokine; Tuberculosis; Co-infection; HIV; mtb; Interferon gamma release assay; QFT; latent TB infection; Quantiferon; active TB; regulatory T cell; Mycobacterium tuberculosis; intereferon-gamma release assay
• ISSN: 1472-9792; 1873-281X; 1873-281X
• DOI: 10.1016/j.tube.2015.05.001

Mycobacterium tuberculosis (Mtb) infects nearly 2 million people annually and is the most common cause of death in HIV-infected individuals. Tuberculosis (TB) diagnostics cater to HIV-uninfected individuals in non-endemic countries, are expensive, slow, and lack sensitivity for those most affected. Patterns of soluble immune markers from Mtb-stimulated immune cells are not well defined in HIV co-infection. We assessed immune differences between HIV-infected and HIV-uninfected individuals with active TB utilizing IFNγ-based QuantiFERON®-TB Gold In-Tube (QFT) testing in Nairobi, Kenya. Excess QFT supernatants were used to measure cytokine and chemokine responses by a 17-plex bead array. Mtb/HIV co-infected participants were significantly less likely to be QFT+ (47.2% versus 84.2% in the HIV-uninfected group), and demonstrated lower expression of all cytokines except for IFNα2. Receiver operator characteristic analyses identified IL-1α as a potential marker of co-infection. Among HIV-infected individuals, CD4+ T cell count correlated weakly with the expression of several analytes. Co-expression analysis highlighted differences in immune profiles between the groups. These data suggest that there is a unique and detectable Mtb-specific immune response in co-infection. A better understanding of Mtb immunology can translate into much needed immunodiagnostics with enhanced sensitivity in HIV-infected individuals, facilitating their opportunity to obtain live-saving treatment.