Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice

Fleur Schaper, Mirjan M van Timmeren, Arjen Petersen, Gerda Horst, Marc Bijl, Pieter C Limburg, Johanna Westra, Peter Heeringa

High Mobility Group Box 1 (HMGB1) is a nuclear DNA binding protein which acts as an alarmin when secreted. HMGB1 is increased in SLE and might represent a potential therapeutic target. We investigated whether treatment with a 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 weeks 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 two weeks blood was drawn and urine was collected at week 7, 11 and 17. Mice were sacrificed at 17 weeks for complete disease evaluation. Plasma HMGB1 and anti-HMGB1 levels were increased in MRL/lpr mice compared to control MRL/MPJ mice. There were no differences in albuminuria, urine HMGB1 and plasma levels of complement C3, anti-dsDNA and pro-inflammatory cytokines between untreated and treated mice at any time point. Lupus nephritis of mice treated with anti-HMGB1 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. Treatment with monoclonal anti-HMGB-1 antibody 2G7 does not affect development of lupus nephritis, disease progression or pro-inflammatory cytokines levels in MRL/lpr mice. This indicates that blocking of HMGB1 by this neutralizing antibody does not affect lupus nephritis in MRL/lpr mice.