Tubular basement membrane immune complex deposition is associated with activity and progression of lupus nephritis: a large multicenter Chinese study

Lupus. 2018 Apr;27(4):545-555. doi: 10.1177/0961203317732407. Epub 2017 Sep 27.

Abstract

Tubulointerstitial injury is found frequently in lupus nephritis. Immune complex deposits can occur in the tubular basement membranes (TBMs), although its significance in lupus nephritis patients remains unclear. This study assessed the clinical and prognostic features of lupus nephritis patients with TBM deposits in a large Chinese multicenter cohort. Complete data were collected from 195 patients with renal biopsy-proven lupus nephritis diagnosed in the Peking University First Hospital as the discovery cohort. A total of 102 lupus nephritis patients were enrolled from another four centers as the validation cohort. The status of TBM deposits was retrospectively assessed using electron microscopy, and the associations of the deposits with clinical data, pathological characteristics and renal outcomes were further analyzed. The percentage of positive TBM deposits was nearly 30% in the lupus nephritis patients. Using immuno-gold labeling, we found that 10/10 patients were positive for IgG, 7/10 were C3d positive, 6/10 were C1q positive, and 1/10 were C4d positive. Patients with TBM deposits presented with more active features, including a higher SLEDAI score (SLE Disease Activity Index) ( p < 0.001), higher serum creatinine level ( p = 0.001) and lower serum C3 level ( p < 0.001). These patients also presented with higher scores for most renal pathological indices, including the total activity indices score ( p < 0.001) and total chronicity indices score ( p = 0.001). TBM deposits affected renal outcomes in the univariate Cox hazards regression analysis (HR = 4.2, 95% CI = 1.3-14.3, p = 0.02). In conclusion, TBM deposits were common in lupus nephritis patients and correlated closely with the clinical disease activity and renal outcome.

Keywords: SLE; electron microscopy; lupus nephritis; pathological classification; renal outcome; tubular basement membranes (TBM) deposits.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antigen-Antibody Complex / immunology*
  • Antigen-Antibody Complex / ultrastructure
  • Biopsy
  • Chi-Square Distribution
  • China
  • Complement C1q / analysis
  • Complement C3d / analysis
  • Complement C4b / analysis
  • Female
  • Glomerular Basement Membrane / drug effects
  • Glomerular Basement Membrane / immunology*
  • Glomerular Basement Membrane / ultrastructure
  • Humans
  • Immunoglobulin G / analysis
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney Tubules / drug effects
  • Kidney Tubules / immunology*
  • Kidney Tubules / ultrastructure
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology
  • Male
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Multivariate Analysis
  • Peptide Fragments / analysis
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Severity of Illness Index
  • Young Adult

Substances

  • Antigen-Antibody Complex
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Peptide Fragments
  • Complement C1q
  • Complement C3d
  • Complement C4b
  • complement C4d