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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31822e0d15
Epidemiology and Prevention

Natural Killer Cell Activation Distinguishes Mycobacterium tuberculosis–Mediated Immune Reconstitution Syndrome From Chronic HIV and HIV/MTB Coinfection

Conradie, Francesca MD*; Foulkes, Andrea S. PhD; Ive, Prudence MD*; Yin, Xiangfan MS; Roussos, Katerina BSc*; Glencross, Deborah K. MD§; Lawrie, Denise MSc§; Stevens, Wendy MD§; Montaner, Luis J. DVM, PhD; Sanne, Ian MD*; Azzoni, Livio MD, PhD

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Abstract

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.

© 2011 Lippincott Williams & Wilkins, Inc.

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