BAFF and APRIL expression as an autoimmune signature of membranous nephropathy

Abstract

BackgroundBased on the fact that B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have a regulatory role in B cell biology, excessive levels of these cytokines can promote autoimmune pathogenesis. However, the expression and implication remain unresolved in cases of membranous nephropathy (MN).ResultsThe plasma BAFF levels of the primary MN patients were higher than those of healthy controls but lower than those of secondary MN patients, whereas the APRIL levels were similar between the MN patients and healthy controls. The BAFF levels were higher in relapse cases, whereas the APRIL levels were higher in the patients who did not experience remission compared with the counterpart patients. The ectopic expression of BAFF and APRIL was observed in the glomeruli or circulating B cells of MN patients, and this high expression trend was similar to that of lupus patients.ConclusionsExpression profile of BAFF and APRIL in MN is similar to that of other autoimmune disease, which affects the kidney outcomes.MethodsPlasma BAFF and APRIL levels were measured upon kidney biopsy in patients with primary (n = 89) and secondary MN (n = 13), and the results were compared with the levels in healthy controls (n = 111). The kidney outcomes (e.g., remission and relapse) were traced for the median of 3 years. Aberrant expression of the cytokines was evaluated in the kidney and circulating B cells using immunohistochemistry and flow cytometry analyses, respectively.

Expression of BAFF, APRIL, and cognate receptor genes in lupus nephritis and potential use as urinary biomarkers

“…Therefore, it is necessary to identify non-invasive biomarkers that can be easily obtained and reflect current renal inflammation [ 34 ]. Over the last two decades, many clinical studies have demonstrated the presence of molecules associated with B-cell activation in the serum [ 29 , [35] , [36] , [37] ] and kidney tissues [ 24 , 26 , 28 , 38 ] of active LN patients. One study demonstrated that serum BAFF level was lower in SLE patients with nephrotic-range proteinuria than in SLE patients with less severe proteinuria.…”

“…Urinary BAFF mRNA was detectable in only a minority of patients (28.57%), mainly of class III and IV, and showed no correlation with other parameters of lupus activity or renal function, consistent with previous studies [ 25 , 30 ]. In contrast, we found that BAFF was detectable by immunohistochemistry in the majority of 52 kidney biopsy samples from LN patients [ 26 ]. Furthermore, patients with class IV LN exhibited the highest glomerular BAFF expression, and expression was correlated with activity index (r ​= ​0.4647, p ​= ​0.0001).…”

“…Several animal model studies have demonstrated pathogenic roles for BAFF, APRIL, and their receptors in SLE and LN, and human clinical studies have demonstrated immunohistochemical expression of BAFF in glomeruli and tubular epithelial cells [ [24] , [25] , [26] , [27] , [28] , [29] ]. However, there are many obvious advantages of urinary detection.…”

The role of BAFF and APRIL in rheumatoid arthritis

“…BAFF is produced by the activation of radiation-resistant stromal cells, B cells, activated T cells, and most myelogenous cell lines, including monocytes, macrophage, and stimulated neutrophils, TLR9-activated plasmacytoid dendritic cells (DCs) and IL2-activated natural killer cells (Craxton et al, 2003;Gorelik et al, 2003;Krumbholz et al, 2005;Nardelli et al, 2001;Scapini et al, 2003;Vincent et al, 2012). Groom et al, 2002;Han et al, 2018;Hegazy et al, 2010;Kamhieh-Milz et al, 2018;Li et al, 2014;Vosters et al, 2012;Xin et al, 2013). Research shows that BAFF and APRIL are also associated with increased tumor growth and invasion in certain solid tumors such as breast cancer (Pelekanou et al, 2017).…”

“…BAFF and APRIL can maintain the activation of B cells, enhancing autoimmune diseases. Overexpression of BAFF leads to the development of polyclonal B cell, hyperglobulinemia and autoimmunity diseases such as systemic lupus erythematosus (SLE), IgA nephropathy, membranous nephropathy, SS, immune thrombocytopenic purpura, and RA (Elbirt et al, ; J. Groom et al, ; Han et al, ; Hegazy et al, ; Kamhieh‐Milz et al, ; Li et al, ; Vosters et al, ; Xin et al, ). Research shows that BAFF and APRIL are also associated with increased tumor growth and invasion in certain solid tumors such as breast cancer (Pelekanou et al, ).…”