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

Schaper, F., van Timmeren, M. M., Petersen, A., Horst, G., Bijl, M., Limburg, P. C., Westra, J. & Heeringa, P., 13-Jan-2016, In : Molecular medicine. 22, p. 12-21 10 p.

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OBJECTIVE: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)12-21
Number of pages10
JournalMolecular medicine
Volume22
Publication statusPublished - 13-Jan-2016

    Keywords

  • CHROMOSOMAL-PROTEIN 1, MOBILITY GROUP BOX-1, SEPSIS SURVIVORS, CYTOKINE RELEASE, HMGB1, ERYTHEMATOSUS, ARTHRITIS, DISEASE, GLOMERULONEPHRITIS, ACTIVATION

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