Serum IgG binding to human mesangial cells in patients with lupus nephritis and its correlation with disease activity

Abstract

BACKGROUND: Mesangial immunoglobulin deposition is a hallmark in lupus nephritis. We previously demonstrated that human anti-dsDNA antibodies could bind to human mesangial cells (HMC). In this study we investigated the binding activity of serum IgG to HMC and its correlation with clinical parameters in lupus patients. METHODS: Serial serum samples were obtained 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 measured using a cellular ELISA and its correlation with clinical or laboratory parameters investigated. Sera from 23 healthy individuals were used as controls. RESULTS: A total of 189 samples were collected - 48 samples during active and 141 during inactive disease, defined according to clinical assessment. Binding of serum total IgG to HMC was 0.12±0.09, 0.59±0.37 and 0.74±0.43 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 differ in the binding of serum IgG2, IgG3 or IgG4 to HMC. HMC-binding activity of total IgG and IgG1 correlated with anti-dsDNA antibody levels (r=0.26 and 0.39 respectively, P<0.001 for both), and inversely correlated 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 in the patients was 81.3%/39.7% (ROC AUC 0.61, P=0.03) and 83.3%/41.8% (AUC 0.63, P=0.009) respectively. CONCLUSIONS: We conclude that total IgG and IgG1 in the serum of patients with lupus nephritis bind significantly to mesangial cells, especially during flare, and this binding correlated with the level of anti-dsDNA antibodies.