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Clinical Microbiology Reviews, October 2009, p. 651-663, Vol. 22, No. 4
0893-8512/09/$08.00+0     doi:10.1128/CMR.00015-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

Patricia Price,1* David M. Murdoch,2 Upasna Agarwal,3 Sharon R. Lewin,4 Julian H. Elliott,4 and Martyn A. French1 Author Bios

School 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,1 Division of Pulmonary, Allergy, & Critical Care Medicine, Duke University Medical Center, Durham, North Carolina,2 LRS Institute of Tuberculosis and Respiratory Diseases, New Delhi, India,3 Infectious Diseases Unit, Alfred Hospital, Department of Medicine, Monash University, and Burnet Institute, Melbourne, Victoria, Australia4

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.

* Corresponding author. Mailing address: University of Western Australia, Level 2, MRF Building, Rear 50 Murray Street, Perth 6000, Western Australia, Australia. Phone: 618-9224 0378. Fax: 618-9224 0204. E-mail: patricia.price{at}uwa.edu.au

Clinical Microbiology Reviews, October 2009, p. 651-663, Vol. 22, No. 4
0893-8512/09/$08.00+0     doi:10.1128/CMR.00015-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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