TLR9 and BAFF: Their expression in patients with IgA nephropathy

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.

Comparison of probiotic lactobacilli and bifidobacteria effects, immune responses and rotavirus vaccines and infection in different host species

“…B cell responses, including activation of intestinal B cells and RV specific IgA Ab titers were enhanced in vaccinated, probiotic colonized piglets compared to uncolonized, vaccinated piglets post-virulent human RVA challenge (Kandasamy et al, 2014). The latter effect coincided with increased TLR9 expression (see above), and according to the previous reports, TLR9 and BAFF up-regulation may be associated with increased IgA levels (Li et al, 2014), and may represent synergistic sensing of probiotics and RV by innate immune cells leading to increased IgA levels. Further, T cell responses, specifically ileal T regulatory cells, and systemic IFNγ producing T cell responses, were increased in probiotic colonized and vaccinated compared to uncolonized vaccinated piglets (Chattha et al, 2013b).…”

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

“…BAFF has been recognized as a biomarker that is associated with clinical and histopathological features [43] . In our previous studies, we revealed that high levels of BAFF can promote IgA CSR and the secretion of aberrantly glycosylated IgA1 [20,26,44] . TLR3-BAFF axis, first mentioned in the field rheumatoid arthritis, has supported in vivo that TLR3-BAFF can induce AID expression and Ig class-switching in B cells [45,46] .…”

“…Peripheral blood mononuclear cells (PBMCs) were isolated as previously described [26] . For urine collection, rats were immobilized above the metabolic cages.…”

A proliferation‐inducing ligand increase precedes IgA nephropathy recurrence in kidney transplant recipients

“…B‐cell‐activating factor (BAFF) and a proliferation‐inducing ligand (APRIL) are proteins of the TNF superfamily that interact through 3 receptors (BAFF‐R, TACI, and BCMA) of B cells contributing to their differentiation to memory B cells and plasma cells . High expression of both proteins has been reported in autoimmune diseases such as systemic lupus erythematosus and appears to be involved in the pathogenesis of IgAN as a stimulus for Gd‐IgA1 production . On the other hand, α‐defensins are peptides that act as effectors of innate immunity against microorganisms and also have a role on adaptive immunity.…”