title: Complement receptor of the immunoglobulin superfamily reduces murine lupus nephritis and cutaneous disease.
abstract: Complement activation takes place in autoimmune diseases and accounts for tissue inflammation. Previously, complement inhibition has been considered for the treatment of SLE. Complement receptor of the immunoglobulin superfamily (CRIg) is a selective inhibitor of the alternative pathway of complement and a soluble form reverses established inflammation and bone destruction in experimental autoimmune arthritis. We asked whether specific inhibition of the alternative pathway could inhibit autoimmunity and/or organ damage in lupus-prone mice. Accordingly, we treated lupus-prone MRL/lpr mice with a soluble form of CRIg (CRIg-Fc) and we found that it significantly diminished skin lesions, proteinuria and pyuria, and kidney pathology. Interestingly, serum levels of anti-DNA antibodies were not affected despite the fact that serum complement 3 (C3) levels increased significantly. Immunofluorescent staining of kidney tissues revealed a reduction in staining intensity for C3, IgG, and the macrophage marker Mac-2. Thus our data show that inhibition of the alternative pathway of complement controls skin and kidney inflammation even in the absence of an effect on the production of autoantibodies. We propose that CRIg should be considered for clinical trials in patients with systemic lupus erythematosus.
authors.affiliation: Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Lieberman
authors.affiliation: Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mizui
authors.affiliation: Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Angèle
authors.initials: A
authors.lastname: Nalbandian
authors.affiliation: Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Bossé
authors.affiliation: Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: José C
authors.initials: JC
authors.lastname: Crispín
authors.affiliation: Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: gtsokos@bidmc.harvard.edu.
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000187:drug effects / Q000276:immunology; D003176:Complement C3 / Q000187:drug effects / Q000276:immunology; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008178:Lupus Erythematosus, Cutaneous / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011507:Proteinuria / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology*; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D003176:Complement C3; D011951:Receptors, Complement; C509992:VSIG4 protein, mouse
keywords: Complement receptor of immunoglobulin (CRIg/VSIG4/Z39IG); Complement system; Glomerulonephritis; MRL/lpr animals; Systemic lupus erythematosus (SLE)