Evaluation of C4d expression and staining patterns by immunohistochemistry in renal biopsy samples with focal segmental glomerulosclerosis and minimal change disease

Ann Diagn Pathol. 2024 Jun:70:152281. doi: 10.1016/j.anndiagpath.2024.152281. Epub 2024 Feb 13.

Abstract

Introduction: C4d is an activation product of lectin pathway of complement. Glomerular deposition of C4d is associated with poor prognosis in different types of immune-related glomerulonephritis. The present study was conducted to investigate expression level of C4d and its staining pattern in renal biopsy of patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) by immunohistochemistry method.

Materials and methods: In this retrospective cross-sectional study, renal biopsy specimens from 46 samples of MCD, 47 samples of FSGS, and 15 samples without glomerular disease as the controls, were subjected to immunohistochemistry staining with C4d. Demographic characteristics and information obtained from light and electron microscopy (EM) of patients were also extracted from their files.

Results: C4d positive staining was observed in 97.9 % of FSGS and 43.5 % of MCD samples, which showed a statistically significant difference (P < 0.001). The sensitivity and specificity of C4d expression for diagnosing FSGS were 97.9 % and 56.5 %, respectively. There was no significant correlation between C4d expression and any of the light and electron microscopy findings, including presence of foam cells, mesangial matrix expansion, interstitial fibrosis and tubular atrophy, and basement membrane changes in MCD patients. Also, no significant correlation was observed between C4d expression and clinical symptoms of proteinuria or prolonged high level of creatinine in patients with MCD.

Discussion and conclusion: The expression of C4d marker had a good sensitivity and negative predictive value in the diagnosis of FSGS.

Keywords: C4d; Focal segmental glomerulosclerosis; Immunohistochemistry; Minimal change disease.

MeSH terms

  • Adolescent
  • Adult
  • Biopsy / methods
  • Complement C4b* / metabolism
  • Cross-Sectional Studies
  • Female
  • Glomerulosclerosis, Focal Segmental* / diagnosis
  • Glomerulosclerosis, Focal Segmental* / metabolism
  • Glomerulosclerosis, Focal Segmental* / pathology
  • Humans
  • Immunohistochemistry* / methods
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Male
  • Middle Aged
  • Nephrosis, Lipoid* / diagnosis
  • Nephrosis, Lipoid* / metabolism
  • Nephrosis, Lipoid* / pathology
  • Peptide Fragments / analysis
  • Peptide Fragments / metabolism
  • Retrospective Studies
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Complement C4b
  • complement C4d
  • Peptide Fragments