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.

CONCLUSION:

In IgAN patients, expression levels of tonsillar TLR9 and TLR9 SNP were well correlated with the efficacy of tonsillectomy with SPT.

• Authors: Daisuke Sato, Yusuke Suzuki, Tatsuya Kano, Hitoshi Suzuki, Joe Matsuoka, Hidenori Yokoi, Satoshi Horikoshi, Katsuhisa Ikeda, Yasuhiko Tomino
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 27 Issue 3 Pg. 1090-7 (Mar 2012) ISSN: 1460-2385 [Electronic] England
• PMID: 21778277 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• TLR9 protein, human
• Toll-Like Receptor 9
• Prednisolone

Topics

• Adult
• B-Lymphocytes (metabolism)
• Blotting, Western
• Case-Control Studies
• Dendritic Cells (metabolism)
• Female
• Flow Cytometry
• Fluorescence
• Glomerulonephritis, IGA (complications, metabolism, therapy)
• Hematuria (etiology, metabolism, therapy)
• Humans
• Male
• Palatine Tonsil (surgery)
• Polymorphism, Single Nucleotide (genetics)
• Prednisolone (therapeutic use)
• Proteinuria (etiology, metabolism, therapy)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Toll-Like Receptor 9 (genetics, metabolism)
• Tonsillectomy