Journal article
HLA Class I restricted CD8+ and Class II restricted CD4+ T cells are implicated in the pathogenesis of nevirapine hypersensitivity
AIDS, Vol.28(13), pp.1891-1901
2014
Abstract
Objectives: This study sought to examine nevirapine hypersensitivity (NVP HSR) phenotypes and their relationship with differing major histocompatibility complex (MHC) Class I and Class II alleles and the associated CD4+ and CD8+ T-cell NVP-specific responses and their durability over time.
Methods: A retrospective cohort study compared HIV-positive patients with NVP HSR, defined by fever and hepatitis and/or rash, with those tolerant of NVP for more than 3 months. Covariates included class I (HLA-A, B, C) and class II (HLA-DR) alleles. Cellular studies examined NVP-specific CD4+ and CD8+ T-cell responses by interferon-gamma (IFNγ) ELISpot assay and intracellular cytokine staining (ICS).
Results: NVP HSR occurred in 19 out of 451 (4%) NVP-exposed individuals between March 1993 and December 2011. HLA associations were phenotype dependent with HLA-DRB1∗01 : 01 associated with hepatitis (P = 0.02); HLA-B∗35 : 01 and HLA-Cw4 associated with cutaneous NVP HSR (P = 0.001, P = 0.01), and HLA-Cw∗08 was associated with NVP HSR with eosinophilia (P = 0.04) and multisystemic NVP HSR (P = 0.02). NVP-specific INFγ responses waned significantly more than 3 months from the original reaction and were diminished or completely abrogated when either CD4+ or CD8+ T cells were depleted from the peripheral blood mononuclear cells culture.
Conclusion: The association of specific class I and II allele pairings with specific phenotypes of NVP HSR, and cellular studies showing both CD4+ and CD8+ T-cell NVP-specific responses suggest that specific combinations of NVP reactive class I restricted CD8+ and class II restricted CD4+ T cells contribute to the immunopathogenesis of NVP HSR.
Details
- Title
- HLA Class I restricted CD8+ and Class II restricted CD4+ T cells are implicated in the pathogenesis of nevirapine hypersensitivity
- Authors/Creators
- N.M. Keane (Author/Creator) - Princess Margaret Hospital for ChildrenR.K. Pavlos (Author/Creator)E. McKinnon (Author/Creator)A. Lucas (Author/Creator)C. Rive (Author/Creator)C.C. Blyth (Author/Creator) - School of Paediatrics and Child HealthD. Dunn (Author/Creator)M. Lucas (Author/Creator) - School of Pathology and Laboratory MedicineS. Mallal (Author/Creator)E. Phillips (Author/Creator)
- Publication Details
- AIDS, Vol.28(13), pp.1891-1901
- Publisher
- Lippincott Williams & Wilkins Ltd.
- Identifiers
- 991005541308007891
- Copyright
- © 2014 Wolters Kluwer Health
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.265 Dermatology - Skin Allergies
- 1.265.1140 Drug Hypersensitivity
- Web Of Science research areas
- Immunology
- Infectious Diseases
- Virology
- ESI research areas
- Immunology