Premium
Metabolic and immunologic risk factors for sulfonamide hypersensitivity in retroviral infection
Author(s) -
Wong Yat Yee,
Johnson Brian,
Trepanier Lauren
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.619.6
Subject(s) - simian immunodeficiency virus , immunology , biology , antigen , gene , sulfonamide , antigen presentation , immune system , virology , t cell , chemistry , genetics , stereochemistry
HIV infected patients have a high risk of hypersensitivity (HS) reactions to trimethoprim/ sulfamethoxazole (TMP/SMX). To understand this, simian immunodeficiency virus (SIV)‐infected rhesus macaques were used to explore possible metabolic and immunologic risk factors. We hypothesized that pathways affecting sulfamethoxazole disposition might be altered by SIV infection. Liver biopsies were obtained from three SIVmac239‐infected male macaques and three non‐infected controls for a whole‐transcript gene expression array experiment. 138 genes were significantly differentially expressed (P < 0.005), with 114 genes up‐regulated and 24 genes down‐regulated. No sulfonamide biotransformation genes, to include CYP2C8, CYP2C9, CYB5R3, NAT2, or glutathione synthetic pathways, were differentially expressed. However, multiple genes involved in antigen processing, to include ubiquitination and proteasomal degradation, were significantly up‐regulated up to10‐fold. Genes involved in antigen presentation were up‐regulated by 1.7‐2.3 fold (P < 0.003). These preliminary data suggest that acquired risk of sulfonamide HS in human retroviral infection may not be due to changes in drug biotransformation, but in the antigen processing and presentation, primarily ubiquitination. Funded by R01 GM100784.