title: Down-regulation of TLR2, 3, 9 and Signaling Mediators, MyD88 and TRIF, Gene Transcript Levels in Patients with Kawasaki Disease Treated with IVIG.
abstract: Kawasaki disease (KD) is an acute febrile systemic vasculitis of childhood characterized by elevated levels of inflammatory mediators at the acute stage. High-dose intravenous immunoglobulin (IVIG) is well accepted as a conventional therapy for KD. The aim of the present study was to determine the expression level of Toll like receptors (TLRs) and their corresponding signaling mediators in PBMCs of IVIG-treated KD patients. TLR2, 3, 9 and signaling mediators, MyD88 and TRIF transcript levels were determined in PBMCs from 31 KD patients, before (acute phase), 2 weeks later (sub-acute phase) and 6 weeks later (convalescent phase) of IVIG therapy using real time PCR. The mean age of the patients was 3.6 years and 65% of subjects were male and 35% were female. 20 age-matched irrelevant febrile patients and 20 healthy subjects were included as control groups. Elevated levels of TLR2, MyD88, and TRIF gene transcripts were observed in the PBMCs at acute phase of untreated KD patients in compression with normal subjects. IVIG therapy resulted in significant decrease in TLR2, 3 and 9 (60-90%) as well as MyD88 and TRIF (60-70%) transcripts following 2 and 6 weeks. With Regard to significant up-regulation of MyD88 and TRIF at the acute phase of KD, our findings suggest TLR signaling pathway potential in KD pathogenesis and may also support the assumption of an infectious background in KD. Down-regulation of TLR members and corresponding mediators in IVIG treated patient suggest general TLR pathway suppression as a novel anti-inflammatory mechanism of IVIG.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran and Department of Pediatrics, Kermanshah University of Medical Sciences, Kermanshah, Iran dr_mormd@yahoo.com.
authors.forename: Seyed Hamidreza
authors.initials: SH
authors.lastname: Mortazavi
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran aminr@sums.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Amin
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran alyasins@sums.ac.ir.
authors.forename: Soheyla
authors.initials: S
authors.lastname: Alyasin
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran Kashefs@sums.ac.ir.
authors.forename: Sara
authors.initials: S
authors.lastname: Kashef
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Karimimh@sums.ac.ir.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Karimi
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Babaeim@sums.ac.ir.
authors.forename: Maryam
authors.initials: M
authors.lastname: Babaei
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran Younesiv@sums.ac.ir.
authors.forename: Vahid
authors.initials: V
authors.lastname: Younesi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis*; D014158:Transcription, Genetic; D059467:Transcriptome / Q000187:drug effects
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016756:Immunoglobulins, Intravenous; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C470409:TICAM1 protein, human; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9