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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
CXCL10
HIV
Interferon gama
Interleucina-18
Imunidade
Tuberculose
Tuberculose
Síndrome Inflamatória da reconstituição imunológica
CXCL10
HIV
Interferon-g
Interleukin-18
Interleukin-18 binding protein
sCD14
Tuberculosis-associated immune
Reconstitution inflammatory syndrome
Tuberculosis
Author
Affilliation
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Bethesda, Maryland, USA
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia / Faculty of Medicine. Tropical Infectious Diseases Research and Education Centre. Department of Medical Microbiology. Kuala Lumpur, Malaysia
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia / University of Malaya Medical Centre. Infectious Disease Unit. Department of Medicine. Kuala Lumpur, Malaysia
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia / University of Malaya Medical Centre. Infectious Disease Unit. Department of Medicine. Kuala Lumpur, Malaysia
National Institute for Research in Tuberculosis. Chennai, India
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia / University of Malaya Medical Centre. Infectious Disease Unit. Department of Medicine. Kuala Lumpur, Malaysia
National Institute for Research in Tuberculosis. Chennai, India
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Bethesda, Maryland, USA
Macfarlane Burnet Institute for Medical Research and Public Health Centre for Biomedical Research. Melbourne / The Alfred Hospital. Infectious Diseases Unit. Melbourne / Monash University. Department of Infectious Diseases. Melbourne
University of Western Australia. School of Pathology and Laboratory Medicine. Australia / Royal Perth Hospital and PathWest Laboratory Medicine. Department of Clinical Immunology. Perth, Western Australia, Australia
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Bethesda, Maryland, USA
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia / Faculty of Medicine. Tropical Infectious Diseases Research and Education Centre. Department of Medical Microbiology. Kuala Lumpur, Malaysia
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia / University of Malaya Medical Centre. Infectious Disease Unit. Department of Medicine. Kuala Lumpur, Malaysia
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia / University of Malaya Medical Centre. Infectious Disease Unit. Department of Medicine. Kuala Lumpur, Malaysia
National Institute for Research in Tuberculosis. Chennai, India
University of Malaysia. Faculty of Medicine. Centre of Excellence for Research in AIDS. Kuala Lumpur, Malaysia / University of Malaya Medical Centre. Infectious Disease Unit. Department of Medicine. Kuala Lumpur, Malaysia
National Institute for Research in Tuberculosis. Chennai, India
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Bethesda, Maryland, USA
Macfarlane Burnet Institute for Medical Research and Public Health Centre for Biomedical Research. Melbourne / The Alfred Hospital. Infectious Diseases Unit. Melbourne / Monash University. Department of Infectious Diseases. Melbourne
University of Western Australia. School of Pathology and Laboratory Medicine. Australia / Royal Perth Hospital and PathWest Laboratory Medicine. Department of Clinical Immunology. Perth, Western Australia, Australia
Abstract
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 timepoint,
in a case–control study of Malaysian HIV patients with paradoxical or unmasking
TB-IRIS (n¼15), TB no IRIS (n¼14), and no TB or IRIS (n¼15). Findings for interleukin-
18 were verified in another cohort of patients with paradoxical TB-IRIS (n¼26) and
their controls (n¼22) 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 in Portuguese
Terapia antirretroviralCXCL10
HIV
Interferon gama
Interleucina-18
Imunidade
Tuberculose
Tuberculose
Síndrome Inflamatória da reconstituição imunológica
Keywords
Antiretroviral therapyCXCL10
HIV
Interferon-g
Interleukin-18
Interleukin-18 binding protein
sCD14
Tuberculosis-associated immune
Reconstitution inflammatory syndrome
Tuberculosis
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