RESUMO
We report the molecular and hematological identifications of two novel δ-globin gene mutations found in Guangxi Zhuang Autonomous Region, China. Capillary electrophoresis of the proband showed 1.3% Hb A2, accompanied by a minor unknown peak (0.7%) within the Z1 zone. High-performance liquid chromatography also revealed the presence of 1.5% Hb A2 and a 0.6% unknown peak. Routine genetic testing (Gap-PCR and reverse dot-blot hybridization) for common α-thalassemia was performed, and no mutations were observed. Sanger sequencing identified a heterozygous mutation for GAC > AAC at codon 79 (HBD:c.238G > A) and G > A at polyA + 70 (HBD:c.*200G > A) of the δ-globin gene. This variant was named Hb A2-Guangxi [δ79 (EF3) AspâAsn, HBD:c.238G > A] after the geographic origin of the proband.
RESUMO
AIM: To study the mechanism underlying the IL-12-induced cytotoxic function of NK cells to Jurkat cells. METHODS: NK cells from peripheral blood mononuclear cells (PBMCs) were purified by magnetic sorting and stimulated with or without IL-12. The expression of genes on IL-12-treated and non-IL-12-treated NK cells was analyzed by gene chips and the expression of cytolytic molecules was evaluated by flow cytometry. RESULTS: Seventeen genes were up- (5/17) or down-regulated (12/17) on IL-12-treated NK cells compared with non-IL-12-treated NK cells (fold change≥10). IL-12-induced expression of TRAIL on NK cells mediated the cytotoxicity to Jurkat cells. The expression of TRAIL on subsets of CD56(+);CD16(+); and CD56(-);CD16(+); NK cells significantly increased after the stimulation with IL-12 and Jurkat cells expressed high level of TRAIL receptor 2 (TRAIL-R2). Importantly, the neutralizing mAbs against TRAIL (RIK-2) significantly inhibited the cytotoxicity of NK cells induced by IL-12. CONCLUSION: The expression of TRAIL on human NK cells induced by IL-12 was one of the major mechanisms of cytotoxicity to Jurkat cells.