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Plasma interleukin-18 levels are a biomarker of innate immune responses that predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome.

Tan HY, Yong YK, Andrade BB, Shankar EM, Ponnampalavanar S, Omar SF, Narendran G, Kamarulzaman A, Swaminathan S, Sereti I, Crowe SM, French MA
aFaculty of Medicine, Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia bNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA cFaculty of Medicine, Trop


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-gamma 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.

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  • Journal: AIDS
  • Published: 05/01/2015
  • Volume: 29
  • Issue: 4
  • Pagination: 421-431

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