Binding activity of serum immunoglobulin G to renal proximal tubular epithelial cells and its clinical correlation in lupus nephritis

Abstract

INTRODUCTION AND AIMS: In vitro data suggested that immunoglobulin G (IgG) from lupus nephritis (LN) patients could bind to proximal renal tubular epithelial cells (PTEC), but its clinical relevance remained to be defined. METHODS: The binding activities of IgG and its subclasses to PTEC were measured with cellular ELISA in 189 serial serum samples from 23 Class III/IV±V LN patients (48 during renal flares, 141 during remission), and compared with samples from 64 patients with non-lupus glomerular diseases (NLGD) and 23 healthy controls. The binding indices of serum IgG to PTEC were expressed as OD. RESULTS: Total IgG PTEC-binding indices were 0.34±0.16, 0.29±0.16, 0.62±0.27 and 0.83±0.38 in healthy controls, NLGD, LN patients during remission, and LN patients during renal flare (P<0.001, remission vs. renal flare; P<0.001, healthy controls or NLGD vs. LN during remission or renal flare). PTEC-binding index for IgG1 was 0.09 ±0.05, 0.16±0.12, 0.44±0.34 and 0.71±0.46 for the corresponding groups (P<0.001, remission vs. renal flare; P<0.001, healthy controls or NLGD vs. LN during remission or renal flare). No significant binding to PTEC was observed for IgG2, IgG3 or IgG4. Sixteen of 48 episodes (33.3%) of nephritic flares, despite clinical response to immunosuppressive therapies, showed persistent seropositivity (mean duration 9.4±3.1 months) for PTEC-binding IgG. Total IgG and IgG1 PTEC-binding demonstrated a positive association with anti-dsDNA titres (r=0.34 and 0.52 respectively, P<0.001 for both), but a negative correlation with C3 level (r=-0.26 and -0.50 respectively, P=0.002 and <0.001). Sensitivity/specificity of PTEC-binding index in predicting renal flares was 45.8%/80.1% for total IgG (ROC AUC 0.630, P=0.007) and 87.5%/35.5% for IgG1 (ROC AUC 0.615, P=0.018). IgG1 PTEC-binding index correlated with tubulo-interstitial inflammation score in renal biopsies from corresponding patients. CONCLUSIONS: Total IgG and IgG1 PTEC-binding index in LN patients correlated with clinical and serological activity, and in combination could predict LN flares.