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

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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

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All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Han, S. S., Yang, S. H., Choi, M., Kim, H. R., Kim, K., Lee, S., Moon, K. C., Kim, J. Y., Lee, H., Lee, J. P., Jung, J. Y., Kim, S., Joo, K. W., Lim, C. S., Kang, S. W., Kim, Y. 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