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Review

Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

Patricia Price, David M. Murdoch, Upasna Agarwal, Sharon R. Lewin, Julian H. Elliott, Martyn A. French
Patricia Price
1School of Pathology and Laboratory Medicine, University of Western Australia, and Department of Clinical Immunology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Western Australia, Australia
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  • For correspondence: patricia.price@uwa.edu.au
David M. Murdoch
2Division of Pulmonary, Allergy, & Critical Care Medicine, Duke University Medical Center, Durham, North Carolina
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Upasna Agarwal
3LRS Institute of Tuberculosis and Respiratory Diseases, New Delhi, India
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Sharon R. Lewin
4Infectious Diseases Unit, Alfred Hospital, Department of Medicine, Monash University, and Burnet Institute, Melbourne, Victoria, Australia
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Julian H. Elliott
4Infectious Diseases Unit, Alfred Hospital, Department of Medicine, Monash University, and Burnet Institute, Melbourne, Victoria, Australia
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Martyn A. French
1School of Pathology and Laboratory Medicine, University of Western Australia, and Department of Clinical Immunology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Western Australia, Australia
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DOI: 10.1128/CMR.00015-09
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SUMMARY

SUMMARY Up to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathological characteristics of IRD associated with viral infections suggest different pathogenic mechanisms. For example, IRD associated with varicella-zoster virus or JC polyomavirus infection correlate with a CD8 T-cell response in the central nervous system. Exacerbations or de novo presentations of hepatitis associated with hepatitis C virus (HCV) infection following ART may also reflect restoration of pathogen-specific immune responses as titers of HCV-reactive antibodies rise in parallel with liver enzymes and plasma markers of T-cell activation. Correlations between immunological parameters assessed in longitudinal sample sets and clinical presentations are required to illuminate the diverse immunological scenarios described collectively as IRD. Here we present salient clinical features and review progress toward understanding their pathogeneses.

  • Copyright © 2009 American Society for Microbiology
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Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms
Patricia Price, David M. Murdoch, Upasna Agarwal, Sharon R. Lewin, Julian H. Elliott, Martyn A. French
Clinical Microbiology Reviews Oct 2009, 22 (4) 651-663; DOI: 10.1128/CMR.00015-09

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Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms
Patricia Price, David M. Murdoch, Upasna Agarwal, Sharon R. Lewin, Julian H. Elliott, Martyn A. French
Clinical Microbiology Reviews Oct 2009, 22 (4) 651-663; DOI: 10.1128/CMR.00015-09
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  • Article
    • SUMMARY
    • INTRODUCTION
    • MYCOBACTERIUM TUBERCULOSIS IRD: ALWAYS AN EXAGGERATED IMMUNE RESPONSE, BUT DIFFERENT MANIFESTATIONS SUGGEST DISTINCT MECHANISMS
    • CRYPTOCOCCAL IRD: SEVERE CONSEQUENCES OF A HIGH ANTIGEN LOAD IN THE CENTRAL NERVOUS SYSTEM
    • IRD ASSOCIATED WITH HSV OR VZV INFECTION MAY BE MEDIATED BY CYTOTOXIC LYMPHOCYTES
    • IRD MANIFESTED AS CMV RETINITIS OR VIRAL ENCEPHALOMYELITIS: A SEARCH FOR THE CYTOKINES
    • IRD ASSOCIATED WITH JCV INFECTION OF THE BRAIN
    • IRD MAY PRESENT AS LEE FOLLOWING INITIATION OF ART IN HIV-HBV-COINFECTED PATIENTS
    • ART MAY ALLOW IMMUNOLOGICAL CONTROL OF HCV, BUT THIS MAY DAMAGE THE LIVER
    • CONCLUSIONS: SOME PIECES BELONG IN ANOTHER JIGSAW PUZZLE
    • ACKNOWLEDGMENTS
    • REFERENCES
    • Author Bios
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KEYWORDS

Immune Reconstitution Inflammatory Syndrome

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