Binding of serum IgG to human mesangial cells and its correlation with disease activity in patients with lupus nephritis

Abstract

BACKGROUND/PURPOSE: Lupus nephritis is hallmarked by mesangial deposition of immunoglobulins, which result in subsequent glomerular injury and altered renal functions. Our group had previously demonstrated that human anti-dsDNA antibodies could bind to human mesangial cells (HMC) and this binding activity correlated with disease activity. In this study we assessed the binding activity to HMC by the serum IgG and its subclasses in lupus nephritis patients. Their associations with clinical and laboratory parameters in lupus nephritis patients were also evaluated. METHODS: Serial serum samples were retrieved from 23 patients with biopsy-proven diffuse proliferative lupus nephritis over a mean follow-up of 74 months. Binding activity (expressed as OD) of total serum IgG and its subclasses (IgG1, IgG2, IgG3, IgG4) to HMC was ascertained with a cellular ELISA and its correlation with clinical or laboratory parameters examined. Sera from 23 healthy individuals were used as controls. Sensitivity/specificity of total IgG or IgG1 binding to HMC in the prediction of renal flare was calculated and ROC curves constructed. RESULTS: A total of 189 samples were analyzed - 48 samples during active and 141 during inactive disease, defined according to clinical assessment (SLEDAI > =10 as active and < = 4 as inactive). Binding of serum total IgG to HMC was 0.12±0.09, 0.59±0.37 and 0.74±0.42 OD for healthy controls, inactive lupus, and active lupus respectively (P = 0.023 active vs inactive, P < 0.001 controls vs active or inactive disease). Binding of serum IgG1 to HMC was 0.05±0.05, 0.41±0.38 and 0.55±0.40 OD for the three groups respectively (P = 0.037 active vs inactive, P < 0.001 controls vs active or inactive disease). Controls and lupus patients did not vary in the binding of serum IgG2, IgG3 or IgG4 to HMC. Total IgG and IgG1 HMC-binding activity correlated with anti-dsDNA levels (r_0.26 and 0.39 respectively, P < 0.001 for both), and inversely with C3 levels (r = -0.17 and -0.45 respectively, P < 0.05 for both). No correlation was observed between IgG binding to HMC and clinical parameters such as serum creatinine, albumin, or proteinuria. Sensitivity/specificity of total IgG or IgG1 binding to HMC in the prediction of renal flare was 81.3%/39.7% (ROC AUC 0.61, P = 0.03) and 83.8%/41.8% (AUC 0.63, P = 0.009) respectively. CONCLUSION: There is significant total IgG and IgG1 mesangial cell-binding activity in the sera of patients with lupus nephritis, especially during active disease, and this binding correlated with the anti-dsDNA antibodies levels.