Mesangial immune complex glomerulonephritis due to complement factor D deficiency

Kidney Int. 2007 Jun;71(11):1142-7. doi: 10.1038/sj.ki.5002235. Epub 2007 Apr 4.

Abstract

Complement factor D is a serine protease essential for the activation of the alternative pathway and is expressed in the kidney, adipocytes, and macrophages. Factor D is found at relatively high levels in glomeruli suggesting that this component of the complement cascade could influence renal pathophysiology. In this study, we utilize mice with a targeted deletion of the activating complement factor D gene and compare these results to mice with targeted deletion of the inhibitory complement factor H gene. Eight-month-old mice with a deleted factor D gene spontaneously develop albuminuria and have reduced creatinine clearance due to mesangial immune complex glomerulonephritis. These mesangial deposits contain C3 and IgM. In contrast to the mesangial location of the immune deposits in the factor D-deficient mice, age-matched factor H-deficient mice develop immune deposits along the glomerular capillary wall. Our observations suggest that complement factor D or alternative pathway activation is needed to prevent spontaneous accumulation of C3 and IgM deposits within the mesangium. Our studies show that the complement factor D gene knockout mice are a novel model of spontaneous mesangial immune complex glomerulonephritis.

Publication types

  • Comparative Study

MeSH terms

  • Albuminuria
  • Animals
  • Antigens, Differentiation / metabolism
  • Capillaries / immunology
  • Capillaries / metabolism
  • Capillaries / ultrastructure
  • Complement C3 / immunology
  • Complement C3 / metabolism
  • Complement Factor D / deficiency*
  • Complement Factor D / genetics
  • Complement Factor H / deficiency
  • Complement Factor H / genetics
  • Creatinine / blood
  • Creatinine / urine
  • Female
  • Fluorescein-5-isothiocyanate
  • Fluorescent Antibody Technique, Indirect
  • Fluorescent Dyes
  • Genotype
  • Glomerular Mesangium / chemistry
  • Glomerular Mesangium / immunology
  • Glomerular Mesangium / pathology
  • Glomerular Mesangium / ultrastructure
  • Glomerulonephritis / genetics
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Histocytochemistry
  • Immune Complex Diseases / genetics
  • Immune Complex Diseases / immunology*
  • Immune Complex Diseases / pathology*
  • Immunoglobulin M / immunology
  • Immunoglobulin M / metabolism
  • Immunohistochemistry
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / ultrastructure
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antigens, Differentiation
  • Complement C3
  • Fluorescent Dyes
  • Immunoglobulin M
  • monocyte-macrophage differentiation antigen
  • Complement Factor H
  • Creatinine
  • Complement Factor D
  • Fluorescein-5-isothiocyanate