Plasma interleukin-18 levels are a biomarker of innate immune responses that predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome.
Tan, H.Y.; Yong, Y.K.; Andrade, B.B.; Shankar, E.M.; Ponnampalavanar, S.; Omar, S.F.; Narendran, G.; Kamarulzaman, A.; Swaminathan, S.; Sereti, I.; Crowe, S.M.; French, M.A.
AIDS; 2015; 29; 421-431.
Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes increased production of proinflammatory chemokines and cytokines, including interleukin-18, which is a signature cytokine of the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared plasma levels of interleukin-18 and other biomarkers of monocyte/macrophage activation in the prediction and characterization of TB-IRIS.
Methods: Biomarkers were assayed pre-ART and during TB-IRIS, or equivalent time point, in a case–control study of Malaysian HIV patients with paradoxical or unmasking TB-IRIS ( n =15), TB no IRIS ( n =14), and no TB or IRIS ( n =15). Findings for interleukin- 18 were verified in another cohort of patients with paradoxical TB-IRIS ( n =26) and their controls ( n =22) from India .
Results: Interleukin-18 was higher in TB-IRIS patients pre-ART and during the event in both Malaysian patients ( P < 0.0001) and Indian patients ( P < 0.01). CXCL10 was higher pre-ART ( P < 0.001), mainly in paradoxical TB-IRIS patients, and during TB-IRIS ( P < 0.001), whereas CXCL8 was only higher during TB-IRIS ( P < 0.001). Soluble(s) CD14 was increased in all patients with HIV/TB coinfection pre-ART and during TB-IRIS or equivalent time-point, compared with patients without TB. In contrast, interferon- g was lower before and during TB-IRIS. By receiver operating curve analysis, CXCL10, and/or interleukin-18 pre-ART were predictive of TB-IRIS.
Conclusion: Plasma interleukin-18 levels pre-ART are candidate biomarkers for predicting paradoxical and unmasking TB-IRIS and should be investigated for risk stratification and elucidation of disease pathogenesis.
Keywords: Antiretroviral therapy; CXCL10; HIV; interferon- g , interleukin-18; interleukin-18 binding protein; sCD14; tuberculosis-associated immune reconstitution inflammatory syndrome; tuberculosis
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