RESUMEN
To examine the association between human leukocyte antigen (HLA) and nevirapine (NVP)- and efavirenz (EFV)-induced cutaneous adverse reactions in human immunodeficiency virus (HIV) patients, we conducted a case-control study at our center consisting of 96 patients. Patients were further assigned based on the occurrence of cutaneous adverse events and the drugs involved. All patients were subjected to next generation sequencing (NGS)-based screening with focus on HLA phenotype, including the presence of HLA-B, HLA-C, and HLA-DRB1. Our data indicated that the HLA-C*01:02:01 allele presence was observed in 47.4% (18/38) of patients in the EFV-hypersensitivity group compared with 18.9% (7/30) in the control group [odds ratio (OR) = 5.837; 95% confidence interval (CI) = 1.727-19.722, p = .005]. In contrast, the occurrence of HLA-DRB1*08:03 was found to be significantly lower in the EFV-hypersensitivity group (4/38, 10.5%) compared with the corresponding control group (12/37, 32.4%) (OR = 0.148; 95% CI = 0.035-0.625, p = .009). In addition, the HLA-DRB1*04:05:01 antigen was expressed more frequently in the NVP-hypersensitivity group (23.8%, 5/21) compared with the control group (10.8%, 4/37) (OR = 7; 95% CI = 1.265-38.793, p = .026). Our data not only revealed a significant association between HLA-C*01:02:01 and EFV-induced cutaneous adverse reactions but may also shed light on defining the treatment for Chinese HIV patients.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Antígenos de Histocompatibilidad Clase I , Nevirapina , Humanos , Alelos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Estudios de Casos y Controles , Pueblos del Este de Asia , Antígenos de Histocompatibilidad Clase I/genética , VIH/genética , Infecciones por VIH/tratamiento farmacológico , Antígenos HLA , Antígenos HLA-C/genética , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/uso terapéutico , Nevirapina/efectos adversos , Hipersensibilidad a las Drogas/genéticaRESUMEN
Background: JinGuanLan (JGL) formula is a traditional Chinese medicine (TCM) developed by the Department of Pharmacology at the First Hospital of Lanzhou University. The network pharmacology approach was applied to determine the potential active compounds, therapeutic targets, and main pathways of the JGL formula to evaluate its application value in acne vulgaris. Methods: Data on the active compounds and their related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Acne vulgaris-related targets were searched from the Online Mendelian Inheritance in Man (OMIM) database, GeneCards Database, Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), and DisGeNET Database. Targets intersecting between JGL- and acne vulgaris-related targets were chosen as potential therapeutic targets. The protein-protein interaction (PPI) network of potential therapeutic targets was visualized using Cytoscape software based on the PPI data collected from the STRING database. Three topological features, namely, "Degree," "MCC," and "EPC" of each node in the PPI network were calculated using the cytoHubba plugin of Cytoscape to excavate the core targets. R program was used for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the potential therapeutic targets. Finally, the compound-target-pathway network was constructed. Result: Among the 148 active compounds that were identified, quercetin and kaempferol showed the highest degree of target interaction and thus may play essential roles in the pharmacological effect of the JGL formula for acne treatment. Among the 97 potential therapeutic targets that were screened out, the 6 core targets were TNF, JUN, IL6, STAT3, MAPK1, and MAPK3. A total of 2260 terms of GO enrichment analysis were obtained, including 2090 for biological processes (BP), 37 for cellular components (CC), and 133 for molecular function (MF). A total of 156 enriched KEGG pathways were identified, including TNF, IL-17, Th17 cell differentiation, MAPK, PI3K-Akt, T cell receptor, and Toll-like receptor signalling pathways. Conclusion: This work showed that the JGL formula might reverse the pathological changes associated with acne vulgaris through its antiinflammatory effect and regulate the excessive lipogenesis in sebaceous glands via different signalling pathways. This new drug has application value and is worthy of further research and development.