The role of TNF superfamily member 13 in the progression of IgA nephropathy

Seung Seok Han, Seung Hee Yang, Murim Choi, Hang Rae Kim, Kwangsoo Kim, Sangmoon Lee, Kyung Chul Moon, Joo Young Kim, Hajeong Lee, Jung Pyo Lee, Ji Yong Jung, Sejoong Kim, Kwon Wook Joo, Chun Soo Lim, Shin Wook Kang, Yon Su Kim, Dong Ki Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

TNF superfamilymember 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.

Original languageEnglish
Pages (from-to)3430-3439
Number of pages10
JournalJournal of the American Society of Nephrology
Volume27
Issue number11
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Immunoglobulin A
Galactose
Genetic Polymorphisms
Chronic Kidney Failure
B-Lymphocytes
RNA Sequence Analysis
Glycosyltransferases
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Polymerase Chain Reaction
Enzymes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Han, S. S., Yang, S. H., Choi, M., Kim, H. R., Kim, K., Lee, S., ... Kim, D. K. (2016). The role of TNF superfamily member 13 in the progression of IgA nephropathy. Journal of the American Society of Nephrology, 27(11), 3430-3439. https://doi.org/10.1681/ASN.2015060677
Han, Seung Seok ; Yang, Seung Hee ; Choi, Murim ; Kim, Hang Rae ; Kim, Kwangsoo ; Lee, Sangmoon ; Moon, Kyung Chul ; Kim, Joo Young ; Lee, Hajeong ; Lee, Jung Pyo ; Jung, Ji Yong ; Kim, Sejoong ; Joo, Kwon Wook ; Lim, Chun Soo ; Kang, Shin Wook ; Kim, Yon Su ; Kim, Dong Ki. / The role of TNF superfamily member 13 in the progression of IgA nephropathy. In: Journal of the American Society of Nephrology. 2016 ; Vol. 27, No. 11. pp. 3430-3439.
@article{702add13b5b64313aa36b1f97a70d652,
title = "The role of TNF superfamily member 13 in the progression of IgA nephropathy",
abstract = "TNF superfamilymember 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.",
author = "Han, {Seung Seok} and Yang, {Seung Hee} and Murim Choi and Kim, {Hang Rae} and Kwangsoo Kim and Sangmoon Lee and Moon, {Kyung Chul} and Kim, {Joo Young} and Hajeong Lee and Lee, {Jung Pyo} and Jung, {Ji Yong} and Sejoong Kim and Joo, {Kwon Wook} and Lim, {Chun Soo} and Kang, {Shin Wook} and Kim, {Yon Su} and Kim, {Dong Ki}",
year = "2016",
month = "1",
day = "1",
doi = "10.1681/ASN.2015060677",
language = "English",
volume = "27",
pages = "3430--3439",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "11",

}

Han, SS, Yang, SH, Choi, M, Kim, HR, Kim, K, Lee, S, Moon, KC, Kim, JY, Lee, H, Lee, JP, Jung, JY, Kim, S, Joo, KW, Lim, CS, Kang, SW, Kim, YS & Kim, DK 2016, 'The role of TNF superfamily member 13 in the progression of IgA nephropathy', Journal of the American Society of Nephrology, vol. 27, no. 11, pp. 3430-3439. https://doi.org/10.1681/ASN.2015060677

The role of TNF superfamily member 13 in the progression of IgA nephropathy. / Han, Seung Seok; Yang, Seung Hee; Choi, Murim; Kim, Hang Rae; Kim, Kwangsoo; Lee, Sangmoon; Moon, Kyung Chul; Kim, Joo Young; Lee, Hajeong; Lee, Jung Pyo; Jung, Ji Yong; Kim, Sejoong; Joo, Kwon Wook; Lim, Chun Soo; Kang, Shin Wook; Kim, Yon Su; Kim, Dong Ki.

In: Journal of the American Society of Nephrology, Vol. 27, No. 11, 01.01.2016, p. 3430-3439.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of TNF superfamily member 13 in the progression of IgA nephropathy

AU - Han, Seung Seok

AU - Yang, Seung Hee

AU - Choi, Murim

AU - Kim, Hang Rae

AU - Kim, Kwangsoo

AU - Lee, Sangmoon

AU - Moon, Kyung Chul

AU - Kim, Joo Young

AU - Lee, Hajeong

AU - Lee, Jung Pyo

AU - Jung, Ji Yong

AU - Kim, Sejoong

AU - Joo, Kwon Wook

AU - Lim, Chun Soo

AU - Kang, Shin Wook

AU - Kim, Yon Su

AU - Kim, Dong Ki

PY - 2016/1/1

Y1 - 2016/1/1

N2 - TNF superfamilymember 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.

AB - TNF superfamilymember 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.

UR - http://www.scopus.com/inward/record.url?scp=85021450106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021450106&partnerID=8YFLogxK

U2 - 10.1681/ASN.2015060677

DO - 10.1681/ASN.2015060677

M3 - Article

C2 - 27068226

AN - SCOPUS:85021450106

VL - 27

SP - 3430

EP - 3439

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 11

ER -