Elevated levels of fractalkine expression and accumulation of CD16+ monocytes in glomeruli of active lupus nephritis

Am J Kidney Dis. 2007 Jul;50(1):47-58. doi: 10.1053/j.ajkd.2007.04.012.

Abstract

Background: Fractalkine (Fkn) is a chemokine that affects cells expressing its receptor, CX3CR1, including CD16-positive (CD16+) monocytes/macrophages (CD16+ Mos). The relationship of levels of glomerular Fkn expression and infiltration by CD16+ Mos with the severity and diversity of glomerular lesions in human lupus nephritis is not known.

Study design: Retrospective cross-sectional analysis of variables observed in biopsy specimens.

Settings & participants: 88 patients with systemic lupus erythematosus.

Predictor: Histological class and severity of lupus nephritis according to the International Society of Nephrology/Renal Pathology Society and clinicopathologic factors.

Outcomes: Outcome variables are assays related to the degree of glomerular Fkn expression and CD16+ Mo infiltration.

Measurements: Immunohistological grading of Fkn staining, number of CD16+ Mos, and messenger RNA levels of Fkn and CD16 in glomeruli.

Results: Patients with proliferative lupus nephritis (class III and IV glomeruli) showed significantly greater glomerular Fkn expression and CD16+ Mo counts than those with other classes. Infiltrating CD16+ Mos within glomeruli expressed CX3CR1. Moreover, glomerular Fkn expression significantly correlated with the histopathologic activity index and CD16+ Mo counts, and CD16+ Mo counts significantly correlated with serum levels of blood urea nitrogen, complement (CH50), and anti-DNA antibody; estimated glomerular filtration rate; and urinary protein excretion. Glucocorticoid therapy had a tendency to decrease both glomerular Fkn expression and CD16+ Mo counts.

Limitations: Only frozen biopsy specimens (from 49 patients) were analyzed for the evaluation of glomerular Fkn expression.

Conclusion: Disease activity and proliferative glomerular lupus nephritis lesions are associated with the glomerular Fkn expression and CD16+ Mo accumulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chemokine CX3CL1
  • Chemokines, CX3C / metabolism*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Leukocyte Count
  • Lupus Nephritis / immunology
  • Lupus Nephritis / metabolism*
  • Lupus Nephritis / pathology
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Receptors, IgG / metabolism
  • Retrospective Studies

Substances

  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Membrane Proteins
  • Receptors, IgG