Biomarkers in immune reconstitution inflammatory syndrome: signals from pathogenesis.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Sereti
Irini
I
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. isereti@mail.nih.gov
Rodger
Alison J
AJ
French
Martyn A
MA
D000818:Animals; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000097:blood* / Q000276:immunology* / Q000382:microbiology / Q000821:virology
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D002097:C-Reactive Protein