RGD Reference Report - Toll-like receptor 9 affects severity of IgA nephropathy. - Rat Genome Database

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Toll-like receptor 9 affects severity of IgA nephropathy.

Authors: Suzuki, H  Suzuki, Y  Narita, I  Aizawa, M  Kihara, M  Yamanaka, T  Kanou, T  Tsukaguchi, H  Novak, J  Horikoshi, S  Tomino, Y 
Citation: Suzuki H, etal., J Am Soc Nephrol. 2008 Dec;19(12):2384-95. doi: 10.1681/ASN.2007121311. Epub 2008 Sep 5.
RGD ID: 7246889
Pubmed: PMID:18776126   (View Abstract at PubMed)
PMCID: PMC2588104   (View Article at PubMed Central)
DOI: DOI:10.1681/ASN.2007121311   (Journal Full-text)

Environmental pathogens are suspected to aggravate renal injury in IgA nephropathy (IgAN), but neither underlying mechanisms nor specific exogenous antigens have been identified. In this study, a genome-wide scan of ddY mice, which spontaneously develop IgAN, was performed, and myeloid differentiation factor 88 (MyD88) was identified as a candidate gene for progression of renal injury (chi(2) = 21.103, P = 0.00017). For evaluation of the potential influence of environmental pathogens on progression of renal injury, ddY mice were housed in either conventional or specific pathogen-free conditions. Expression of genes encoding toll-like receptors (TLR) and the signaling molecule MyD88 were quantified by real-time reverse transcription-PCR in splenocytes. Although the housing conditions did not affect the prevalence of IgAN, the severity of renal injuries was higher in the conventionally housed group. Mice that had IgAN and were housed in conventional conditions had higher levels of TLR9 and MyD88 transcripts than mice that had IgAN and were housed in specific pathogen-free conditions. Furthermore, nasal challenge with CpG-oligodeoxynucleotides, which are ligands for TLR9, aggravated renal injury, led to strong Th1 polarization, and increased serum and mesangial IgA. For investigation of whether these results may be generalizable to humans, single-nucleotide polymorphisms in the TLR9 and MyD88 genes were analyzed in two cohorts of patients with IgAN; an association was observed between TLR9 polymorphisms and disease progression. In summary, these findings suggest that activation of the TLR9/MyD88 pathway by common antigens may affect the severity of IgAN.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
IgA glomerulonephritis severityISOTlr9 (Mus musculus)7246889; 7246889DNA more ...RGD 
IgA glomerulonephritis severityIAGP 7246889DNA:SNPs:intron more ...RGD 
IgA glomerulonephritis severityISOTLR9 (Homo sapiens)7246889; 7246889DNA:SNPs:intron more ...RGD 
IgA glomerulonephritis severityIAGP 7246889DNA more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Abnormal renal morphology severityIAGP 7246889DNA:SNPs:intron more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Tlr9  (toll-like receptor 9)

Genes (Mus musculus)
Tlr9  (toll-like receptor 9)

Genes (Homo sapiens)
TLR9  (toll like receptor 9)


Additional Information