Journal
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Volume 58, Issue 3, Pages 309-318Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e31822e0d15
Keywords
Mycobacterium tuberculosis; IRIS; HIV; immune reconstitution; natural killer cells; CD69
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Funding
- NIH/NIAID [RO1 AI069996, RO1 HL107196]
- Commonwealth of Pennsylvania
- Commonwealth Universal Research Enhancement Program
- Pennsylvania Department of Health
- Cancer Center [P30 CA10815]
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Background: With increased access to antiretroviral treatment (ART), immune reconstitution inflammatory syndrome (IRIS) in Mycobacterium tuberculosis (MTB)-infected populations remains a clinical challenge. We studied a cross-sectional cohort of HIV-infected subjects in Johannesburg (South Africa) to help define the immune correlates that best distinguish IRIS from ongoing MTB cases. Methods: We studied HIV+ subjects developing MTB-related unmasking tuberculosis-related immune reconstitution inflammatory syndrome (uTB-IRIS) after ART initiation; control groups were subjects with HIV and HIV/tuberculosis-coinfected subjects with comparable ART treatment. Testing was conducted with whole blood-based 4-color flow cytometry and plasma-based Luminex cytokine assessment. Results: Natural killer cell activation, C-reactive protein, and interleukin 8 serum concentration were significantly higher in uTB-IRIS subjects compared with both control groups. In addition, all MTB-coinfected subjects, independent of clinical presentation, had higher neutrophils and T-cell activation, together with lower lymphocytes, CD4(+) T-cell, and myeloid dendritic cell counts. Using conditional inference tree analysis, we show that elevated natural killer cell activation in combination with lymphocyte count characterizes the immunological profile of uTB-IRIS. Conclusion: Our results support a role for innate immune effectors in the immunopathogenesis of unmasking MTB-related IRIS and identify new immune parameters defining this pathology.
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