title: Tonsillar TLR9 expression and efficacy of tonsillectomy with steroid pulse therapy in IgA nephropathy patients.
abstract: BACKGROUND
  Patients with IgA nephropathy (IgAN) often show aggravation of renal injury with macroscopic hematuria after mucosal infections, especially tonsillitis. We previously demonstrated the important role of mucosal Toll-like receptor 9 (TLR9) activation in the pathogenesis of murine IgAN. Moreover, a single nucleotide polymorphism (SNP) in TLR9 was significantly associated with pathological severity in human IgAN. In this study, we investigated correlations between tonsillar TLR9 messenger RNA expression, TLR9 SNP genotypes and clinical outcomes following tonsillectomy with steroid pulse therapy (SPT) in IgAN patients.
  
  
  METHODS
  Tonsillar TLR9 expression was examined in IgAN (n = 49) and control (n = 15) patients who had undergone tonsillectomy. The correlations between tonsillar TLR9 expression level, TLR9 SNP genotypes and clinical outcomes after tonsillectomy with SPT were examined.
  
  
  RESULTS
  High expression of tonsillar TLR9 was observed in ∼23% of IgAN patients. These patients showed stronger and earlier remission of hematuria and proteinuria than those with low TLR9 expression. Patients with the TT genotype of TLR9 SNP (rs352140) had more severe renal damage than those with other genotypes. Patients whose serum IgA level decreased more than average after tonsillectomy (large ΔIgA) showed higher cumulative remission rates of proteinuria than patients with a smaller decrease in these levels (small ΔIgA). CT/CC genotypes were more dominant and tonsillar TLR9 expressions significantly higher in large ΔIgA patients than in small ΔIgA patients.
  
  
  CONCLUSIONS
  In IgAN patients, expression levels of tonsillar TLR9 and TLR9 SNP were well correlated with the efficacy of tonsillectomy with SPT.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Joe
authors.initials: J
authors.lastname: Matsuoka
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yokoi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D006417:Hematuria / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D006801:Humans; D008297:Male; D014066:Palatine Tonsil / Q000601:surgery*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011239:Prednisolone / Q000627:therapeutic use*; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000378:metabolism; D014068:Tonsillectomy
chemical_list: D012333:RNA, Messenger; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D011239:Prednisolone