期刊
JOURNAL OF INFECTION
卷 82, 期 2, 页码 245-252出版社
W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2020.11.032
关键词
Tuberculosis; Immune test; Interleukin-6; M. tuberculosis latency antigens
资金
- German Research Foundation (DFG) [JA 1479/9-1]
- graduate school 'Molecules of Infection-3' - 'Juergen-Manchot foundation'
- MRC [MR/J01477X/1] Funding Source: UKRI
IL-6 showed the highest sensitivity for detecting tuberculosis patients and asymptomatic contacts. Latency-associated antigens Rv2628 and Rv1733 increased concentrations of IFN gamma, IP-10, and IL-22 in asymptomatic contacts. The combination of IFN gamma induced by Rv2628/Rv1733 and IL-6 induced by IGRA-antigen was optimal for classifying tuberculosis patients and asymptomatic contacts.
Objectives: IFN gamma-release assays (IGRAs) used for diagnosis of Mycobacterium (M.) tuberculosis infection have limited sensitivity. Alternative cytokines and M. tuberculosis latency-associated antigens may improve immune-based tests. Methods: Multiplex cytokine analyses was done in culture supernatants after 6-day in vitro restimulation with M. tuberculosis IGRA and latency-associated antigens (i.e. Rv2628, Rv1733) in tuberculosis patients (n = 22) and asymptomatic contacts (AC)s (n = 20) from Ghana. Results: Four cytokines (i.e. IFN gamma, IP-10, IL-22 and IL-6) were significantly increased after IGRA-antigen specific restimulation. IFN gamma, IP-10, and IL-22 correlated positively and showed no differences between the study groups whereas IGRA-antigen induced IL-6 was significantly higher in tuberculosis patients. Using adjusted IGRA criteria, IL-6 showed the highest sensitivity for detection of tuberculosis patients (91%) and ACs (85%) as compared to IFN gamma, IP-10, and IL-22. Rv2628 and Rv1733 restimulation induced significantly higher IFN gamma, IP-10, and IL-22 concentrations in ACs. Combined antigen/cytokine analyses identified study group specific patterns and a combination of Rv2628/Rv1733 induced IFN gamma with IGRA-antigen induced IL-6 was optimal for classification of tuberculosis patients and ACs (AUC: 0.92, p<0.0001). Conclusions: We demonstrate the potency of alternative cytokines, especially IL-6, and latency-associated antigens Rv1733/Rv2628 to improve detection of M. tuberculosis infection and to classify tuberculosis patients and healthy contacts. (C) 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
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