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

作者：Conradie Francesca; Foulkes Andrea S; Ive Prudence; Yin Xiangfan; Roussos Katerina; Glencross Deborah K; Lawrie Denise; Stevens Wendy; Montaner Luis J; Sanne Ian; Azzoni Livio^*

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2011, 58(3): 309-318.

DOI：10.1097/QAI.0b013e31822e0d15

• Mycobacterium tuberculosis
• IRIS
• HIV
• immune reconstitution
• natural killer cells
• CD69

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.

• 出版日期2011-11-1