New insights into the pathogenesis of IgA nephropathy: do toll like receptor 9-B cell activation factor-IgA class switching recombination signaling axis induce IgA hyper-production?
IgA nephropathy (IgAN) has become the most common form of primary glomerular disease worldwide. So far, it is still not very clear about the exact pathogenesis of IgAN, thus has no specific therapy. Generally mesangial deposition of IgA, especially polymeric IgA1 (pIgA1), suggests to be the initiating event in the pathogenesis of IgAN. In addition to decreased IgA clearance, IgA over production may also participate in the pathogenesis of IgAN. IgA class switching recombination (CSR) played key role during the process of IgA production. Stimulated with hemolytic streptococcus, tonsillar mononuclear cells (TMCs) of patients with IgAN presented with increased levels of Ia-Ca and activation-induced cytidine deaminase (AID), which are significant for IgA CSR. Human B cells and plasmacytoid dendritic cells express Toll-like receptor (TLR)-9, whose natural ligands are unmethylated cytosine-guanine dinucleotide (CpG) motifs characteristic of bacterial DNA (CpG-DNA). Unmethylated deoxycytidylic-deoxyguanosine oligodeoxynucleotide (CpG-ODN) is able to mimic the immunostimulatory activity of microbial DNA. Study found a significant increase in B cell activation factor (BAFF) production when tonsillar mononuclear cells stimulated with CpG-ODN in patients with IgAN. BAFF can induce germline Cα gene expression, AID expression, and IgA class switching in a CD40-independent manner. Therefore, it could be hypothesized that in IgAN there may exist TLR9-BAFF-IgA CSR axis, which induces excessive IgA production. If the hypothesis is correct, it could be of great significance for pathogenesis of IgAN elucidate and IgAN treatment.
Department of Nephropathy, Renal Research Institute, Hunan Key Laboratory of Kidney Disease and Blood Purification, Second Xiangya Hospital, Central South University , Changsha , China and.
Yuyuan
Y
Liu
Hong
H
Liu
Youming
Y
Peng
Fuyou
F
Liu
D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000209:etiology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching; D012141:Respiratory Tract Infections / Q000150:complications; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
D053264:B-Cell Activating Factor; D007070:Immunoglobulin A; D051217:Toll-Like Receptor 9
B cell activation factor; IgA; Toll-like receptor 9; class switching recombination; glomerulonephritis