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- W2752859748 abstract "HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions (SCAR) including Steven-Johnson Syndrome/Toxic epidermal Necrolysis (SJS/TEN) and Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms (HSS/DRESS). However, most individuals (97%), who harbor HLA-B*58:01 tolerate allopurinol indicating that other factors contribute to its pathogenesis. Furthermore, HLA-B*58:01 is not phenotype specific with patients developing either SJS/TEN or HSS/DRESS. We performed gene expression studies to determine the molecular processes that confer susceptibility to SCAR and ascertain any differences between SJS/TEN and HSS/DRESS patients. Total RNA was extracted from peripheral blood mononuclear cells of patients with allopurinol-induced SCAR and tolerant controls. Microarrays were performed on 11 RNA samples (4 SJS/TEN, 3 HSS/DRESS, 4 controls). The Partex® genomics suite (v6.6) was used to identify expressed genes and pathways, followed by quantitative real-time PCR (qPCR) on 19 samples (8 SJS/TEN, 4 HSS/DRESS, 7 controls). REST software was used to calculate the relative expression. HLA-B*58:01 was present in all patients and 2 selected controls. Gene profiling showed high expression of the cell cycle-related histone linker H1.5 gene (6.479-fold, P = 0.005) in SCAR patients. Also, high expression of miR146a was observed in HLA-B*58:01 positive controls compared to SCAR patients (3.700-fold, P = 0.33). Comparing the 2 patient groups, TLR7 and TLR4 were downregulated in HSS/DRESS while only low expression of TLR7 was found in SJS/TEN. Furthermore, several genes such as IL-10 (6.345-fold, P = 0.035), MMP8 (9.531-fold, P = 0.021), and MMP9 (5.561-fold, P = 0.032), which encode for alarmins were highly expressed in SJS/TEN. Gene expression studies demonstrate the important role of certain innate immune responses in allopurinol-induced SCAR. These include histone linker H1.5, a crucial factor for dendritic cell maturation and T-cell proliferation; miR146a, a negative regulator of innate immunity and alarmins, chemotactic activators of immune responses. Further studies are being conducted to determine the significance of these findings." @default.
- W2752859748 created "2017-09-15" @default.
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- W2752859748 date "2017-09-01" @default.
- W2752859748 modified "2023-09-27" @default.
- W2752859748 title "P72: GENE PROFILING STUDIES DEMONSTRATE THE ROLE OF INNATE IMMUNE RESPONSES IN ALLOPURINOL-INDUCED SEVERE CUTANEOUS ADVERSE REACTIONS." @default.
- W2752859748 doi "https://doi.org/10.1111/imj.72_13578" @default.
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