TLR9 and BAFF: Their expression in patients with IgA nephropathy

Li,Weiwei; Peng,Xiaofei; Liu,Yuyuan; Liu,Hong; Liu,Fuyou; He,Liyu; Liu,Yang; Zhang,Fan; Guo,Chunyan; Chen,Guochun; Zhang,Lei; Dong,Zheng; Peng,Youming

doi:10.3892/mmr.2014.2359

TLR9 and BAFF: Their expression in patients with IgA nephropathy

Authors:
- Weiwei Li
- Xiaofei Peng
- Yuyuan Liu
- Hong Liu
- Fuyou Liu
- Liyu He
- Yang Liu
- Fan Zhang
- Chunyan Guo
- Guochun Chen
- Lei Zhang
- Zheng Dong
- Youming Peng
View Affiliations

Affiliations: Department of Nephrology, Renal Research Institute, Hunan Key Laboratory of Kidney Disease and Blood Purification, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: July 1, 2014 https://doi.org/10.3892/mmr.2014.2359
Pages: 1469-1474

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Since it was first described in 1968, immunoglobulin (Ig)A nephropathy (IgAN) has become the most commonly diagnosed form of primary glomerular disease worldwide. A number of reports have shown that toll‑like receptor 9 (TLR9) and B‑cell activating factor (BAFF) may be associated with IgAN; however, sufficient evidence has not yet to be delivered. In the present study, serum levels of BAFF as well as TLR9 mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) were assessed. Expression of TLR9 mRNA in PBMCs was examined by quantitative polymerase chain reaction and the TLR9 protein was determined by western blot analysis. The levels of serum BAFF and IgA1 were determined by specific ELISA. Serum levels of BAFF and IgA1 as well as levels of TLR9 mRNA and protein in PMBCs were significantly higher in patients with IgAN compared with patients with minimal glomerular abnormalities (P<0.05, P<0.01, P<0.01 and P<0.01, respectively) and normal controls (P<0.01, P<0.01, P<0.05 and P<0.01, respectively). A correlation and regression analysis was performed to determine the pathogenesis of IgAN. In patients with IgAN, serum levels of BAFF were positively correlated with IgA1 levels (rp, 0.515; P<0.01) and mesangial IgA deposition density (rp, 0.746; P<0.01). Expression levels of TLR9 protein in PBMCs of IgAN patients were positively correlated with levels of serum BAFF (rp, 0.444; P<0.05) and IgA1 (rp, 0.633; P<0.01). These results suggested that overexpression of TLR9 mRNA and protein in PBMCs and elevated levels of serum BAFF may be associated with overexpression of serum IgA1, and, furthermore, may have a role in the development of IgAN.

View Figures

View References

1	D’Amico G: The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 64:709–727. 1987.PubMed/NCBI
2	Appel GB and Waldman M: The IgA nephropathy treatment dilemma. Kidney Int. 69:1939–1944. 2006. View Article : Google Scholar : PubMed/NCBI
3	Barratt J and Feehally J: IgA nephropathy. J Am Soc Nephrol. 16:2088–2097. 2005. View Article : Google Scholar : PubMed/NCBI
4	Julian BA and Novak J: IgA nephropathy: an update. Curr Opin Nephrol Hypertens. 13:171–179. 2004. View Article : Google Scholar
5	Lai KN: Pathogenesis of IgA nephropathy. Nat Rev Nephrol. 8:275–283. 2012. View Article : Google Scholar
6	Suzuki H, Suzuki Y, Narita I, et al: Toll-like receptor 9 affects severity of IgA nephropathy. J Am Soc Nephrol. 19:2384–2395. 2008. View Article : Google Scholar : PubMed/NCBI
7	Goto T, Bandoh N, Yoshizaki T, et al: Increase in B-cell-activation factor (BAFF) and IFN-gamma productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy. Clin Immunol. 126:260–269. 2008. View Article : Google Scholar
8	Suzuki S, Fujieda H, Sunaga H, et al: Immune response of tonsillar lymphocytes to Haemophilus parainfluenzae in patients with IgA nephropathy. Clin Exp Immunol. 119:328–332. 2000. View Article : Google Scholar
9	Fujieda S, Suzuki H, Sunaga, et al: Induction of IgA against Haemophilus parainfluenzae antigens in tonsillar mononuclear cells from patients with IgA nephropathy. Clin Immunol. 95:235–243. 2000.
10	McCluskie MJ, Weeratna RD and Davis HL: Intranasal immunization of mice with CpG DNA induces strong systemic and mucosal responses that are influenced by other mucosal adjuvants and antigen distribution. Mol Med. 6:867–877. 2000.
11	Kajiyama T, Suzuki Y, Kihara M, et al: Different pathological roles of toll-like receptor 9 on mucosal B cells and dendritic cells in murine IgA nephropathy. Clin Dev Immunol. 2011:8196462011. View Article : Google Scholar : PubMed/NCBI
12	Liu H, Peng Y, Liu F, Xiao W, Zhang Y and Li W: Expression of IgA class switching gene in tonsillar mononuclear cells in patients with IgA nephropathy. Inflamm Res. 60:869–878. 2011. View Article : Google Scholar : PubMed/NCBI
13	Krieg AM and Vollmer J: Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity. Immunol Rev. 220:251–269. 2007. View Article : Google Scholar : PubMed/NCBI
14	Krieg AM, Yi AK, Matson S, et al: CpG motifs in bacterial DNA trigger direct B-cell activation. Nature. 374:546–549. 1995. View Article : Google Scholar : PubMed/NCBI
15	Kaisho T and Akira S: Dendritic-cell function in Toll-like receptor- and MyD88-knockout mice. Trends Immunol. 22:78–83. 2001. View Article : Google Scholar : PubMed/NCBI
16	Ashkar AA and Rosenthal KL: Toll-like receptor 9, CpG DNA and innate immunity. Curr Mol Med. 2:545–556. 2002. View Article : Google Scholar : PubMed/NCBI
17	Leadbetter EA, Rifkin IR and Marshak-Rothstein A: Toll-like receptors and activation of autoreactive B cells. Curr Dir Autoimmun. 6:105–122. 2003. View Article : Google Scholar : PubMed/NCBI
18	Schneider P, MacKay F, Steiner V, et al: BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 189:1747–1756. 1999. View Article : Google Scholar : PubMed/NCBI
19	Moore PA, Belvedere O, Orr A, et al: BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 285:260–263. 1999. View Article : Google Scholar : PubMed/NCBI
20	Craxton A, Magaletti D, Ryan EJ and Clark EA: Macrophage- and dendritic cell - dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF. Blood. 101:4464–4471. 2003. View Article : Google Scholar : PubMed/NCBI
21	Scapini P, Nardelli B, Nadali G, Calzetti F, Pizzolo G, Montecucco C and Cassatella MA: A G-CSF-stimulated neutrophils are a prominent source of functional BLyS. J Exp Med. 197:297–302. 2003.PubMed/NCBI
22	Nardelli B, Belvedere O, Roschke V, et al: Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood. 97:198–204. 2001. View Article : Google Scholar : PubMed/NCBI
23	Bergamin F, Vincent IE, Summerfield A and McCullough KC: Essential role of antigen-presenting cell-derived BAFF for antibody responses. Eur J Immunol. 37:3122–3130. 2007. View Article : Google Scholar : PubMed/NCBI
24	Jego G, Pascual V, Palucka AK and Banchereau J: Dendritic cells control B cell growth and differentiation. Curr Dir Autoimmun. 8:124–139. 2005. View Article : Google Scholar : PubMed/NCBI
25	Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P and Cerutti A: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 3:822–829. 2002. View Article : Google Scholar : PubMed/NCBI
26	McCarthy DD, Chiu S, Gao Y, Summers-deLuca LE and Gommerman JL: BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT. Cell Immunol. 241:85–94. 2006. View Article : Google Scholar : PubMed/NCBI
27	Xin G, Shi W, Xu LX, Su Y, Yan LJ and Li KS: Serum BAFF is elevated in patients with IgA nephropathy and associated with clinical and histopathological features. J Nephrol. 26:683–690. 2012. View Article : Google Scholar : PubMed/NCBI
28	Huang H, Peng Y, Liu H, Yang X and Liu F: Decreased CD4⁺CD25⁺ cells and increased dimeric IgA-producing cells in tonsils in IgA nephropathy. J Nephrol. 23:202–209. 2010.
29	Pontarollo RA, Rankin R, Babiuk LA, et al: Monocytes are required for optimum in vitro stimulation of bovine peripheral blood mononuclear cells by non-methylated CpG motifs. Vet Immunol Immunopathol. 84:43–59. 2002. View Article : Google Scholar
30	Fujieda S, Suzuki S, Sunaga H, Yamamoto H, Seki M, Sugimoto H and Saito H: Production of interferon-gamma by tonsillar mononuclear cells in IgA nephropathy patients. Acta Otolaryngol. 120:649–654. 2000. View Article : Google Scholar : PubMed/NCBI
31	Buchanan RM, Popowych Y, Arsic N, et al: B-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and proliferation. Cell Immunol. 271:16–28. 2011. View Article : Google Scholar : PubMed/NCBI
32	Buchanan R, Popowych Y, Dagenais C, et al: Interferon-gamma and B-cell activating factor (BAFF) promote bovine B cell activation independent of TLR9 and T-cell signaling. Vet Immunol Immunopathol. 145:453–463. 2012. View Article : Google Scholar : PubMed/NCBI
33	Ng LG, Ng CH, Woehl B, et al: BAFF costimulation of Toll-like receptor-activated B-1 cells. Eur J Immunol. 36:1837–1846. 2006. View Article : Google Scholar : PubMed/NCBI