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Review
. 2010 Nov;5(6):504-10.
doi: 10.1097/COH.0b013e32833ed774.

Biomarkers in immune reconstitution inflammatory syndrome: signals from pathogenesis

Irini Sereti  1 , Alison J Rodger, Martyn A French
Affiliations
Review

Biomarkers in immune reconstitution inflammatory syndrome: signals from pathogenesis

Irini Sereti et al. Curr Opin HIV AIDS. 2010 Nov.

Abstract

Purpose of review: Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening or unmasking of an infection or neoplasm in HIV-1-infected patients shortly after antiretroviral therapy (ART) initiation. New insights into the pathogenesis of IRIS may help identify biomarkers that could be useful in predicting or diagnosing IRIS.

Recent findings: Studies of immunopathogenesis have shown a signification activation of both innate and adaptive immune responses with elevation of plasma or serum chemokines and cytokines. Markers of inflammation such as C-reactive protein, interferon-inducible protein 10 or interferon γ may be helpful as predictors of IRIS events. In addition, tuberculosis (TB)-associated IRIS is associated with a prominent Th1 response that can be heightened even prior to ART initiation in cases of unmasking TB, and may assist in early diagnosis. Large prospective studies are needed to elucidate the predictive and diagnostic value of IRIS biomarkers and advance them to the clinic.

Summary: Reversal of immunosuppression by ART leads to exaggerated pathogen-specific immune responses (known as IRIS) that appear to be primed prior to therapy. Inflammatory markers, chemokines and cytokines that signify innate and adaptive immune activation are biomarkers that could prove of clinical value after appropriate validation.

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Figures

Figure 1
Figure 1
The immune reconstitution inflammatory syndrome (IRIS) results from the reversal of immunosuppression caused by HIV infection. It is characterized by innate and adaptive immune responses to dead or live pathogens that lead to the release of cytokines and chemokines, which may differ for different types of pathogen. The effects of the cytokines and chemokines produced may include enhancement of Th1 responses (IL-18, IFNγ), recruitment of T cells and NK cells to sites of inflammation (CXCL-10) and production of inflammatory molecules such as CRP (IL-6). One or more of these molecules could be candidate biomarkers for IRIS.
See this image and copyright information in PMC

References

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    1. Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008;8:516–523. - PMC - PubMed
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    1. Rodger AJ, Fox Z, Lundgren JD, Kuller LH, Boesecke C, Gey D, et al. Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection. J Infect Dis. 2009;200:973–983. • Case control study in SMART participants looking at opportunistic disease (OD) events and showing that C-reactive protein and IL-6 were predictors of OD when measured several months prior to the event.

    1. Kalayjian RC, Machekano RN, Rizk N, Robbins GK, Gandhi RT, Rodriguez BA, et al. Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy. J Infect Dis. 2010;201:1796–1805. • Case control study in ART-naïve subjects showing that higher pre-ART levels of Interleukin 6, sTNFR-1 and sCD40L were associated with AIDS or death events that developed at a median of 51 weeks of ART.

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