Germinal center kinase-like kinase (GLK/MAP4K3) expression is increased in adult-onset Still's disease and may act as an activity marker

Abstract

Abstract Background Germinal center kinase-like kinase (GLK, also termed MAP4K3), a member of the MAP4K family, may regulate gene transcription, apoptosis and immune inflammation in response to extracellular signals. The enhanced expression of GLK has been shown to correspond with disease severity in patients with systemic lupus erythematosus. We investigated the role of GLK in the pathogenesis of adult-onset Still's disease, which shares some similar clinical characteristics with systemic lupus erythematosus. Methods The frequencies of circulating GLK-expressing T-cells in 24 patients with active adult-onset Still's disease and 12 healthy controls were determined by flow cytometry analysis. The expression levels of GLK proteins and transcripts were evaluated in peripheral blood mononuclear cells by immunoblotting and quantitative PCR. Serum levels of T helper (Th)17-related cytokines, including IL-1β, IL-6, IL-17 and TNF-α, were measured by ELISA. Results Significantly higher median frequencies of circulating GLK-expressing T-cells were observed in patients with adult-onset Still's disease (31.85%) than in healthy volunteers (8.93%, P P P P P Conclusions Elevated expression levels of GLK and their positive correlation with disease activity in patients with adult-onset Still's disease indicate that GLK may be involved in the pathogenesis and act as a novel activity biomarker of this disease.

Keywords

• Adult-onset Still's disease
• GCK-like kinase (GLK, MAP4K3)
• mitogen-activated protein kinases (MAPKs)
• pathogenesis
• Th17-related cytokines