Anti-F2RL1 monoclonal Antibody, clone 7087

Activated CD8+ T cells play important roles in the pathogenesis of vitiligo. However, driving factors about the activation and migration of CD8+ T cells remain obscure. In this study, we aim to identify differentially expressed genes (DEGs) and uncover potential factors that drive the disease in melanocyte-specific CD8+ T cells in vitiligo. A total of 1147 DEGs were found through transcriptome sequencing in CD8+ T cells from lesional skin of vitiligo patients and normal controls. Based on KEGG pathway enrichment analysis and PPI, 16 upregulated and 23 downregulated genes were identified. Ultimately, 3 genes were figured out after RT-qPCR verification. The mRNA and protein expression levels of PIK3CB, HIF-1 alpha, and F2RL1 were all elevated in CD8+ T cells from peripheral blood in vitiligo. HIF-1 alpha and PIK3CB were significantly increased in lesional skin of vitiligo. Two CpG sites of the HIF-1 alpha promoter were hypomethylated in vitiligo CD8+ T cells. In conclusion, HIF-1 alpha, F2RL1, and PIK3CB may act as novel drivers for vitiligo, which are all closely associated with reactive oxygen species and possibly contribute to the activation and/or migration of melanocyte-specific CD8+ T cells in vitiligo. In addition, we uncovered a potential role for DNA hypomethylation of HIF-1 alpha in CD8+ T cells of vitiligo.

Objectives Glucocorticoids such as dexamethasone have pleiotropic effects, including desired antileukemic, antiinflammatory, or immunosuppressive effects, and undesired metabolic or toxic effects. The most serious adverse effects of dexamethasone among patients with acute lymphoblastic leukemia are osteonecrosis and thrombosis. To identify inherited genomic variation involved in these severe adverse effects, we carried out genome-wide association studies (GWAS) by analyzing 14 pleiotropic glucocorticoid phenotypes in 391 patients with acute lymphoblastic leukemia. Patients and methods We used the Projection Onto the Most Interesting Statistical Evidence integrative analysis technique to identify genetic variants associated with pleiotropic dexamethasone phenotypes, stratifying for age, sex, race, and treatment, and compared the results with conventional single-phenotype GWAS. The phenotypes were osteonecrosis, central nervous system toxicity, hyperglycemia, hypokalemia, thrombosis, dexamethasone exposure, BMI, growth trajectory, and levels of cortisol, albumin, and asparaginase antibodies, and changes in cholesterol, triglycerides, and low-density lipoproteins after dexamethasone. Results The integrative analysis identified more pleiotropic single nucleotide polymorphism variants (P= 1.46x10(-215)), and these variants were more likely to be in gene-regulatory regions ( P= 1.22x10(-6)) than traditional single-phenotype GWAS. The integrative analysis yielded genomic variants (rs2243057 and rs6453253) in F2RL1, a receptor that functions in hemostasis, thrombosis, and inflammation, which were associated with pleiotropic effects, including osteonecrosis and thrombosis, and were in regulatory gene regions. Conclusion The integrative pleiotropic analysis identified risk variants for osteonecrosis and thrombosis not identified by single-phenotype analysis that may have importance for patients with underlying sensitivity to multiple dexamethasone adverse effects. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.