title: Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice.
abstract: High mobility group box 1 (HMGB1) is a nuclear DNA binding protein that acts as an alarmin when secreted. HMGB1 is increased in systemic lupus erythematosus and might represent a potential therapeutic target. We investigated whether treatment with an anti-HMGB1 antibody affects the development of lupus nephritis in MRL/lpr mice. Seven-week-old MRL/lpr mice were injected intraperitoneally twice weekly for 10 wks with 50 μg monoclonal anti-HMGB1 (2G7, mouse IgG2b) (n = 12) or control antibody (n = 11). Control MRL/MPJ mice (n = 10) were left untreated. Every 2 wks, blood was drawn and urine was collected at wk 7, 11 and 17. Mice were sacrificed at 17 wks for complete disease evaluation. Plasma HMGB1 and anti-HMGB1 levels were increased in MRL/lpr mice compared with control MRL/MPJ mice. There were no differences in albuminuria, urine HMGB1 and plasma levels of complement C3, anti-dsDNA and proinflammatory cytokines between untreated and treated mice at any time point. Lupus nephritis of mice treated with anti-HMGB1 monoclonal antibody (mAb) was classified as class III (n = 3) and class IV (n = 9), while mice treated with control mAb were classified as class II (n = 4), class III (n = 2) and class IV (n = 5). IgG and C3 deposits in kidneys were similar in mice treated with anti-HMGB1 mAb or control mAb. In conclusion, treatment with monoclonal anti-HMGB-1 antibody 2G7 does not affect development of lupus nephritis, disease progression or proinflammatory cytokine levels in MRL/lpr mice. This result indicates that blocking of HMGB1 by this neutralizing antibody does not affect lupus nephritis in MRL/lpr mice.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Fleur
authors.initials: F
authors.lastname: Schaper
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Mirjan M
authors.initials: MM
authors.lastname: van Timmeren
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: Petersen
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Gerda
authors.initials: G
authors.lastname: Horst
authors.affiliation: Department of Internal Medicine and Rheumatology, Martini Hospital, Groningen, the Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Bijl
authors.affiliation: Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Limburg
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
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