Background and aims Anti-dsDNA antibody plays a critical role in the pathogenesis of lupus nephritis and contributes to inflammatory and fibrotic processes in the kidney. EDA⁺ spliced variant of fibronectin (EDA⁺ FN), normally only weakly expressed, is markedly increased in pathological conditions. We investigated the effect of human polyclonal anti-dsDNA antibodies on the expression of EDA⁺ FN in proximal tubular epithelial cells (PTEC) and the functional consequence.

Methods EDA⁺ FN expression in human renal biopsies of Class III/IV±V lupus nephritis was assessed by cytochemistry. Cultured PTEC were incubated with control IgG or IgG anti-dsDNA antibodies isolated from lupus nephritis patients for 24 hour and the expression of EDA⁺ FN was investigated. Recombinant human EDA peptide was used to investigate the functional role of EDA⁺ FN in PTEC.

Results The results showed that EDA⁺ FN was absent from normal kidney tissue but was markedly increased in the tubulo-interstitium in lupus nephritis patients. Cultured PTEC constitutively expressed native FN but not EDA⁺ FN. Anti-dsDNA antibodies, compared with serum-free-medium and control IgG, increased EDA⁺ FN expression by 5.8- and 5.6-fold respectively (p<0.05 for both), and the induction was mediated through PI3K and mTOR activation. Exogenous IL-1β and TGF-β1, but not IL-6, IL-8 or MCP-1, induced EDA⁺ FN by 1.8- and 2.3-fold respectively. Recombinant EDA peptide increased native FN, collagen I, laminin and SNAIL expression, but decreased E-cadherin expression, in PTEC.

Conclusions Our data demonstrated a role of EDA⁺ FN in the pathogenesis of tubulo-interstitial disease in lupus nephritis.