title: Age-determined severity of anti-myeloperoxidase autoantibody-mediated glomerulonephritis in mice.
abstract: Anti-neutrophil cytoplasmic antibody associated vasculitis (AAV) is a typical disease of the elderly. In AAV, there is an age-specific increase in disease incidence with age being a predictor of disease outcome. In this study, we aimed to determine the contribution of age to the development of AAV employing a mouse model of anti-myeloperoxidase (MPO) antibody-mediated glomerulonephritis.
  
  
  
  Anti-MPO IgG and lipopolysaccharide (LPS)-mediated glomerulonephritis was induced in 3- and 18-month-old C57Bl6 mice. Clinical and pathological parameters of disease severity, alterations in the immune system and kidney specific changes in these mice were evaluated.
  
  
  
  Eighteen-month-old mice developed increased disease severity upon injection of anti-MPO IgG/LPS compared with 3-month-old mice. This was evidenced by increased albuminuria, more extensive glomerular capillary necrosis and increased glomerular neutrophil accumulation. Glomerular crescent formation was mild in both young and old mice. Old mice displayed higher plasma interleukin-6 levels as well as higher proportions of circulating neutrophils and activated monocytes compared with young mice. In addition, renal mRNA levels of inflammatory genes and endothelial adhesion molecules were higher in 18-month-old mice compared with 3-month-old mice.
  
  
  
  In conclusion, our results indicate that aged mice develop more severe clinical and pathological disease upon induction of anti-MPO IgG/LPS-mediated glomerulonephritis. These findings may be attributed to age-related changes in the immune system as well as in the kidney itself.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Mirjan M
authors.initials: MM
authors.lastname: van Timmeren
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Arjen H
authors.initials: AH
authors.lastname: Petersen
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jill
authors.initials: J
authors.lastname: Moser
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: AnneMieke M H
authors.initials: AM
authors.lastname: Boots
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
mesh_terms: D000375:Aging; D000818:Animals; D001323:Autoantibodies / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology* / Q000473:pathology; D007074:Immunoglobulin G / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000502:physiology*; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D009195:Peroxidase
keywords: ageing; ANCA-associated vasculitis; glomerulonephritis; inflamm-ageing; mouse model