title: The Role of TNF Superfamily Member 13 in the Progression of IgA Nephropathy.
abstract: TNF superfamily member 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.
authors.affiliation: Departments of *Internal Medicine.|Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Seung Seok
authors.initials: SS
authors.lastname: Han
authors.affiliation: Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Biomedical Sciences.
authors.forename: Murim
authors.initials: M
authors.lastname: Choi
authors.affiliation: Biomedical Sciences.|Anatomy, and.
authors.forename: Hang-Rae
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kwangsoo
authors.initials: K
authors.lastname: Kim
authors.affiliation: Biomedical Sciences.
authors.forename: Sangmoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Moon
authors.affiliation: Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Departments of *Internal Medicine.|Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Hajeong
authors.initials: H
authors.lastname: Lee
authors.affiliation: Departments of *Internal Medicine.|Kidney Research Institute, Seoul National University, Seoul, Korea.|Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Jung Pyo
authors.initials: JP
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Gachon University of Medicine and Science, Incheon, Korea; and.
authors.forename: Ji Yong
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Departments of *Internal Medicine.
authors.forename: Sejoong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Departments of *Internal Medicine.|Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.affiliation: Departments of *Internal Medicine.|Kidney Research Institute, Seoul National University, Seoul, Korea.|Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chun Soo
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Shin-Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Departments of *Internal Medicine.|Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Departments of *Internal Medicine, dkkim73@gmail.com.|Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000502:physiology; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000150:complications*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology*; D008297:Male; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood / Q000502:physiology*
chemical_list: D053300:Tumor Necrosis Factor Ligand Superfamily Member 13
keywords: IgA nephropathy; glomerulonephritis; lymphocytes; outcomes