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Irak4 biomarker

Hui Wang, Souhayla El Maadidi, Janett Fischer, Elena Grabski, Sabine Dickhöfer, Sascha Klimosch, Sinead M Flannery, Angela Filomena, Olaf-Oliver Wolz, Nicole Schneiderhan-Marra, Markus W Löffler, Manfred Wiese, Tica Pichulik, Beat Müllhaupt, David Semela, Jean-François Dufour, Pierre-Yves Bochud, Andrew G Bowie, Ulrich Kalinke, Thomas Berg, Alexander N R Weber
UNLABELLED: Patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (IRAK4), a critical signaling mediator in Toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV)...
November 2015: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hui Wang, Sinead M Flannery, Sabine Dickhöfer, Stefanie Huhn, Julie George, Andriy V Kubarenko, Jesus Lascorz, Melanie Bevier, Joschka Willemsen, Tica Pichulik, Clemens Schafmayer, Marco Binder, Bénédicte Manoury, Søren R Paludan, Marta Alarcon-Riquelme, Andrew G Bowie, Asta Försti, Alexander N R Weber
Within innate immune signaling pathways, interleukin-1 receptor-associated kinases (IRAKs) fulfill key roles downstream of multiple Toll-like receptors and the interleukin-1 receptor. Although human IRAK4 deficiency was shown to lead to severe immunodeficiency in response to pyogenic bacterial infection during childhood, little is known about the role of human IRAK2. We here identified a non-synonymous IRAK2 variant, rs35060588 (coding R214G), as hypofunctional in terms of NF-κB signaling and Toll-like receptor-mediated cytokine induction...
August 15, 2014: Journal of Biological Chemistry
Erika Zilahi, Tünde Tarr, Gábor Papp, Zoltán Griger, Sándor Sipka, Margit Zeher
MicroRNA-146a (miR-146a) is a microRNA supposed to regulate innate immune, inflammatory response and antiviral pathway negatively. Recently, its potential use as a biomarker for disease diagnosis, prevention and treatment has become widely investigated. In the current study, we measured the expression of miR-146a/b, and their target genes, IRAK1, IRAK4, TRAF6 in the peripheral mononuclear cells of patients with Sjögren's syndrome (n=21) and healthy controls (n=10) by quantitative reverse transcription polymerase chain reaction...
January 30, 2012: Immunology Letters
Ivana V Yang, Claire M Wade, Hyun Min Kang, Scott Alper, Holly Rutledge, Brad Lackford, Eleazar Eskin, Mark J Daly, David A Schwartz
Innate immunity is the first line of defense against microbial infections. Although polymorphisms in toll-like receptors (TLRs) and downstream signaling molecules (CD14, TLR2, TLR4, TLR5, and IRAK4) affect the innate immune response, these variants account for only a portion of the ability of the host to respond to bacteria, fungi, and viruses. To identify other genes involved in the innate immune response, we challenged 16 inbred murine strains with lipopolysaccharide (LPS) systemically and measured serum concentrations of pro-inflammatory cytokines IL-1beta, IL-6, and TNFalpha, and the chemokine KC 6 hr post-treatment...
December 2009: Genetics
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