Biomarkers in immune reconstitution inflammatory syndrome: signals from pathogenesis

Sereti, Irinia; Rodger, Alison Jb; French, Martyn Ac

doi: 10.1097/COH.0b013e32833ed774
Biomarkers of outcomes of disease, treatment and complications: Edited by H. Clifford Lane and Jens D. Lundgren

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.

aLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

bHIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, UCL Medical School, University College London, London, UK

cSchool of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia

Correspondence to Irini Sereti, 10 Center Drive, Building 10, Room 11B-07A, Bethesda, MD 20892, USA Tel: +1 301 496 5533; fax: +1 301 480 9978; e-mail: isereti@mail.nih.gov

© 2010 Lippincott Williams & Wilkins, Inc.