Journal article
Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal meningitis
HIV Medicine, Vol.9(5), pp.307-316
2008
Abstract
Objectives: A proportion of HIV patients beginning antiretroviral therapy (ART) develop immune restoration disease (IRD). Immunological characteristics of IRD were investigated in a cohort of HIV patients beginning therapy in Kuala Lumpur, Malaysia. Methods: Peripheral blood mononuclear cells were collected at weeks 0, 6, 12, 24 and 48 of ART from five patients experiencing IRD [two with cryptococcal and three with Mycobacterium tuberculosis (Mtb) disease], eight non-IRD controls who had begun ART with CD4 T-cell counts of <100 cells/μL and 17 healthy controls. Leukocytes producing interferon-gamma (IFNγ) were quantified by enzyme-linked immunospot assay after stimulation with purified protein derivative (PPD), early secretory antigenic target-6 (ESAT-6), Cryptococcus neoformans or Cytomegalovirus antigens. Plasma immunoglobulin (IgG) antibodies reactive with these antigens were assessed by enzyme-linked immunosorbent assay. Proportions of activated (HLA-DR hi) and regulatory (CD25 CD127 lo and CTLA-4 +) CD4 T-cells were quantified by flow cytometry. Results: Plasma HIV RNA declined andCD4 T-cell counts rose within 8-27 weeks on ART. Mtb IRD patients displayed elevated IFNγ responses and/or plasma IgG to PPD, but none responded to ESAT-6. Cryptococcal IRD occurred in patients with low baseline CD4 T-cell counts and involved clear IFNγ and antibody responses to cryptococcal antigen. Proportions of activated and regulatory CD4 T-cells declined on ART, but remained higher in patients than in healthy controls. At the time of IRD, proportions of activated CD4 T-cells and regulatory CD4 T-cells were generally elevated relative to other patients. Conclusions: Cryptococcal and Mtb IRD generally coincide with peaks in the proportion of activated T-cells, pathogen-specific IFNγ responses and reactive plasma IgG. IRD does not reflect a paucity of regulatory CD4 T-cells.
Details
- Title
- Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal meningitis
- Authors/Creators
- D.B.A. Tan (Author/Creator)Y.K. Yong (Author/Creator) - University Malaya Medical CentreH.Y. Tan (Author/Creator) - University Malaya Medical CentreA. Kamarulzaman (Author/Creator) - University Malaya Medical CentreL.H. Tan (Author/Creator) - University Malaya Medical CentreA. Lim (Author/Creator) - The University of Western AustraliaI. James (Author/Creator) - Royal Perth HospitalM. French (Author/Creator) - The University of Western AustraliaP. Price (Author/Creator) - Royal Perth Hospital
- Publication Details
- HIV Medicine, Vol.9(5), pp.307-316
- Publisher
- Blackwell Publishing
- Identifiers
- 991005540488807891
- Copyright
- © 2008 British HIV Association
- Murdoch Affiliation
- Centre for Clinical Immunology and Biomedical Statistics
- Language
- English
- Resource Type
- Journal article
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- Citation topics
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- 1.194 Tuberculosis & Leprosy
- 1.194.273 TB Diagnostics & Treatment
- Web Of Science research areas
- Infectious Diseases
- ESI research areas
- Immunology