Immune restoration disease: a consequence of dysregulated immune responses after HAART.
Immune Restoration Diseases (IRD) are a collection of atypical 'opportunistic infections' and inflammatory diseases seen in human immunodeficiency virus (HIV) patients after HIV viraemia is suppressed by highly active antiretroviral therapy (HAART). IRD probably reflect dysregulated immune responses against pre-existing infections by opportunistic pathogens, with different immunopathological mechanisms for different pathogens. For example, mycobacterial IRD are associated with delayed type hypersensitivity (DTH) responses to mycobacterial antigens, whereas patients who experience cytomegalovirus (CMV) IRD have elevated plasma levels of soluble CD30, a marker of a T2 cytokine environment expressed by activated CD8 T-cells. As IRD are often compartmentalised to organs, monitoring serological markers such as pathogen-specific IgG antibody, may be informative, as demonstrated for CMV and hepatitis C virus (HCV)-associated IRD. Genetic studies have provided evidence of distinct immunopathological mechanisms and inherited susceptibility to IRD associated with mycobacterial and herpesviridae infections. The expansion of HAART in the developing world where many HIV patients have low CD4+ T-cell counts and high rates of concomitant infections will place a large number of patients at-risk of developing IRD. It is therefore important to understand the immunopathology so that prevention, diagnosis and treatment can be improved.
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital and School of Surgery and Pathology, University of Western Australia, Perth, Australia. sfstone@cyllene.uwa.edu.au
Shelley F
SF
Stone
Patricia
P
Price
Martyn A
MA
French
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001327:Autoimmune Diseases / Q000209:etiology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D003587:Cytomegalovirus / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D015850:Interleukin-6 / Q000097:blood; D017730:Ki-1 Antigen / Q000097:blood; D009161:Mycobacterium / Q000276:immunology; D018139:Simplexvirus / Q000276:immunology
D019380:Anti-HIV Agents; D015415:Biomarkers; D007074:Immunoglobulin G; D015850:Interleukin-6; D017730:Ki-1 Antigen; D018819:Dipeptidyl Peptidase 4