title: Accelerated nephrotoxic nephritis is exacerbated in C1q-deficient mice.
abstract: C1q deficiency strongly predisposes to the development of systemic lupus erythematosus in humans and mice. We used the model of accelerated nephrotoxic nephritis in C1q-deficient mice to explore the mechanisms behind these associations. C1q-deficient mice developed severe glomerular thrombosis within 4 days of induction of disease, whereas wild-type mice developed mild injury. These findings suggest that C1q protects from immune-mediated glomerular injury. This exacerbated thrombosis was also seen in mice triply deficient in C1q, factor B, and C2, excluding a major pathogenic role for the alternative pathway of complement in this phenomenon. However, these mice did not develop elevated creatinine levels. No exacerbation of accelerated nephrotoxic nephritis was observed in mice doubly deficient in factor B and C2, suggesting a protective role for C1q against renal inflammation that is proximal to C2 activation. There were increased murine IgG deposits, neutrophil numbers, and apoptotic cells in the glomeruli of C1q-deficient mice compared with wild-type mice. Renal expression of genes encoding procoagulant proteins was also enhanced in C1q-deficient mice. The increased IgG deposits and apoptotic cells in the glomeruli of C1q-deficient mice suggest that the exacerbation of disease may be due to a defect in the clearance of immune complexes and/or apoptotic cells from their kidneys.
authors.affiliation: Division of Medicine, Imperial College School of Science, Technology, and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: M G
authors.initials: MG
authors.lastname: Robson
authors.forename: H T
authors.initials: HT
authors.lastname: Cook
authors.forename: M
authors.initials: M
authors.lastname: Botto
authors.forename: P R
authors.initials: PR
authors.lastname: Taylor
authors.forename: N
authors.initials: N
authors.lastname: Busso
authors.forename: R
authors.initials: R
authors.lastname: Salvi
authors.forename: C D
authors.initials: CD
authors.lastname: Pusey
authors.forename: M J
authors.initials: MJ
authors.lastname: Walport
authors.forename: K A
authors.initials: KA
authors.lastname: Davies
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015922:Complement C1q / Q000032:analysis / Q000172:deficiency* / Q000235:genetics*; D003175:Complement C2 / Q000172:deficiency / Q000235:genetics; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D011415:Complement Factor B / Q000172:deficiency / Q000235:genetics; D003170:Complement Pathway, Alternative / Q000235:genetics; D019085:Fluorescent Antibody Technique, Direct; D019084:Fluorescent Antibody Technique, Indirect; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D011817:Rabbits; D013927:Thrombosis / Q000209:etiology / Q000276:immunology / Q000473:pathology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D007074:Immunoglobulin G; C048844:anti-IgG; D015922:Complement C1q; D011415:Complement Factor B