Limits...
A replication study from Chinese supports association between lupus-risk allele in TNFSF4 and renal disorder.

Zhou XJ, Cheng FJ, Qi YY, Zhao MH, Zhang H - Biomed Res Int (2013)

Bottom Line: In genome-wide expression data, TNFSF4 was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies.However, the associations were marginally significant.The detailed mechanisms of its role in pathogenesis will still be further needed.

View Article: PubMed Central - PubMed

Affiliation: Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China.

ABSTRACT
A recent phenotypic association study of genetic susceptibility loci in SLE suggested that TNFSF4 gene might be useful to predict renal disorder in lupus patients. To replicate the association, two single-nucleotide polymorphisms (SNPs: rs2205960 and rs10489265) were genotyped in 814 SLE patients. Correlations between genotypes and TNFSF4 expression were determined. The stainings of TNFSF4 in renal biopsy specimens were checked by immunohistochemistry. The SNPs of TNFSF4 were associated with renal involvement in lupus patients from the Chinese population (P values for rs2205960 and rs10489265 were 0.014 and 0.005 in additive model, resp.). An association between risk genotypes and low C3 levels was also observed (P = 0.034). Functional prediction suggested that rs2205960 had a regulatory feature. The risk alleles seemingly correlated with lower TNFSF4 expression. Strong TNFSF4 expression was detected in lymph nodes and "apparently normal" paratumor renal biopsy but not in renal biopsies from lupus nephritis. In genome-wide expression data, TNFSF4 was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies. However, the associations were marginally significant. Our data firstly replicated the association of TNFSF4 with renal disorder in SLE patients in the Chinese population, which supported that TNFSF4 may act as a marker of lupus nephritis. The detailed mechanisms of its role in pathogenesis will still be further needed.

Show MeSH

Related in: MedlinePlus

Immunohistochemical stainings of TNFSF4. The expression of TNFSF4 in lymph node (a), renal biopsy from patients with one WHO class IV lupus nephritis (b), negative control (c), and a paratumor renal biopsy without histologic abnormalities (d) were shown. As no obvious expression of TNFSF4 was detected in glomeruli, no further comparisons were shown according to genotypes of lupus nephritis.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3713374&req=5

fig2: Immunohistochemical stainings of TNFSF4. The expression of TNFSF4 in lymph node (a), renal biopsy from patients with one WHO class IV lupus nephritis (b), negative control (c), and a paratumor renal biopsy without histologic abnormalities (d) were shown. As no obvious expression of TNFSF4 was detected in glomeruli, no further comparisons were shown according to genotypes of lupus nephritis.

Mentions: In the lymph nodes, TNFSF4 was mainly located in the cytomembrane and in the cytoplasm of positive cells in a circular or linear form. In all of the renal tissues including type I, II, III, IV, and V lupus nephritis, no obvious expression of TNFSF4 was detected in glomeruli, tubules, and vasculature (Figure 2). However, TNFSF4 expression was detected in a granular distribution at part of tubule epithelial cells from a paratumor renal biopsy without any histological abnormalities. It may indicate less TNFSF4 expressions in LN kidney than those in “normal tissues”. Indeed, from a genome-wide gene-expression analysis from kidney biopsy which included larger samples, it was observed that TNFSF4 mRNA expressions were downregulated both in glomeruli (5.61 ± 0.24 versus 5.76 ± 0.18; P = 0.044; 32 LN patients versus 14 controls) and in tubulointerstitium (4.64 ± 0.12 versus 4.72 ± 0.14; P = 0.052; 32 LN patients versus 15 controls) from LN patients compared with those from controls [9].


A replication study from Chinese supports association between lupus-risk allele in TNFSF4 and renal disorder.

Zhou XJ, Cheng FJ, Qi YY, Zhao MH, Zhang H - Biomed Res Int (2013)

Immunohistochemical stainings of TNFSF4. The expression of TNFSF4 in lymph node (a), renal biopsy from patients with one WHO class IV lupus nephritis (b), negative control (c), and a paratumor renal biopsy without histologic abnormalities (d) were shown. As no obvious expression of TNFSF4 was detected in glomeruli, no further comparisons were shown according to genotypes of lupus nephritis.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3713374&req=5

fig2: Immunohistochemical stainings of TNFSF4. The expression of TNFSF4 in lymph node (a), renal biopsy from patients with one WHO class IV lupus nephritis (b), negative control (c), and a paratumor renal biopsy without histologic abnormalities (d) were shown. As no obvious expression of TNFSF4 was detected in glomeruli, no further comparisons were shown according to genotypes of lupus nephritis.
Mentions: In the lymph nodes, TNFSF4 was mainly located in the cytomembrane and in the cytoplasm of positive cells in a circular or linear form. In all of the renal tissues including type I, II, III, IV, and V lupus nephritis, no obvious expression of TNFSF4 was detected in glomeruli, tubules, and vasculature (Figure 2). However, TNFSF4 expression was detected in a granular distribution at part of tubule epithelial cells from a paratumor renal biopsy without any histological abnormalities. It may indicate less TNFSF4 expressions in LN kidney than those in “normal tissues”. Indeed, from a genome-wide gene-expression analysis from kidney biopsy which included larger samples, it was observed that TNFSF4 mRNA expressions were downregulated both in glomeruli (5.61 ± 0.24 versus 5.76 ± 0.18; P = 0.044; 32 LN patients versus 14 controls) and in tubulointerstitium (4.64 ± 0.12 versus 4.72 ± 0.14; P = 0.052; 32 LN patients versus 15 controls) from LN patients compared with those from controls [9].

Bottom Line: In genome-wide expression data, TNFSF4 was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies.However, the associations were marginally significant.The detailed mechanisms of its role in pathogenesis will still be further needed.

View Article: PubMed Central - PubMed

Affiliation: Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China.

ABSTRACT
A recent phenotypic association study of genetic susceptibility loci in SLE suggested that TNFSF4 gene might be useful to predict renal disorder in lupus patients. To replicate the association, two single-nucleotide polymorphisms (SNPs: rs2205960 and rs10489265) were genotyped in 814 SLE patients. Correlations between genotypes and TNFSF4 expression were determined. The stainings of TNFSF4 in renal biopsy specimens were checked by immunohistochemistry. The SNPs of TNFSF4 were associated with renal involvement in lupus patients from the Chinese population (P values for rs2205960 and rs10489265 were 0.014 and 0.005 in additive model, resp.). An association between risk genotypes and low C3 levels was also observed (P = 0.034). Functional prediction suggested that rs2205960 had a regulatory feature. The risk alleles seemingly correlated with lower TNFSF4 expression. Strong TNFSF4 expression was detected in lymph nodes and "apparently normal" paratumor renal biopsy but not in renal biopsies from lupus nephritis. In genome-wide expression data, TNFSF4 was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies. However, the associations were marginally significant. Our data firstly replicated the association of TNFSF4 with renal disorder in SLE patients in the Chinese population, which supported that TNFSF4 may act as a marker of lupus nephritis. The detailed mechanisms of its role in pathogenesis will still be further needed.

Show MeSH
Related in: MedlinePlus