HLA Class I restricted CD8+ and Class II restricted CD4+ T cells are implicated in the pathogenesis of nevirapine hypersensitivity.
AIDS
; 28(13): 1891-901, 2014 Aug 24.
Article
en En
| MEDLINE
| ID: mdl-24911354
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*01ââ01 associated with hepatitis (P = 0.02); HLA-B*35ââ01 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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Antígenos de Histocompatibilidad Clase I
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Linfocitos T CD4-Positivos
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Antígenos de Histocompatibilidad Clase II
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Infecciones por VIH
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Linfocitos T CD8-positivos
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Nevirapina
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Hipersensibilidad a las Drogas
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
AIDS
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2014
Tipo del documento:
Article