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.
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.
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.
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.
*Clinical HIV Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa
†School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA
‡The Wistar Institute, Philadelphia, PA
§Department of Molecular Medicine and Hematology, University of the Witwatersrand, Johannesburg, South Africa
Supported partially by NIH/NIAID grant RO1 AI069996 to L. Azzoni and NIH/NIAID grant RO1 HL107196 to A. S. Foulkes. Additional support was provided by The Philadelphia Foundation (Robert I. Jacob's Fund), The Stengel-Miller Family, AIDS funds from the Commonwealth of Pennsylvania and from the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health, and by a Cancer Center Grant (P30 CA10815). This publication was made possible through core services and support from the Penn Center for AIDS Research (CFAR), an NIH-funded program (P30 AI 045008).
Results contained in this article were communicated, in part, at the 18th Conference on Retroviruses and Opportunistic Infections, February 27, to March 2, 2011, Boston, MA.
The authors have no conflicts of interest to disclose.
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Correspondence to: Livio Azzoni, MD, PhD, HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, 3601 Spruce St, Philadelphia, PA 19104 (e-mail: email@example.com).
Received May 11, 2011
Accepted July 15, 2011