Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice
We evaluated the efficacy of a neutralizing anti-high mobility group box 1 (HMGB1) monoclonal antibody in MRL/lpr lupus-prone mice. The anti-HMGB1 monoclonal antibody (5 mg/kg weight) or class-matched control immunoglobulin G2a (IgG2a) was administered intravenously twice a week for 4–15 weeks. Urin...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050117300712 |
| _version_ | 1819130961850269696 |
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| author | Haruki Watanabe Katsue S. Watanabe Keyue Liu Sumie Hiramatsu Sonia Zeggar Eri Katsuyama Noriko Tatebe Akiya Akahoshi Fumiaki Takenaka Takahisa Hanada Masaru Akehi Takanori Sasaki Ken-ei Sada Eiji Matsuura Masahiro Nishibori Jun Wada |
| author_facet | Haruki Watanabe Katsue S. Watanabe Keyue Liu Sumie Hiramatsu Sonia Zeggar Eri Katsuyama Noriko Tatebe Akiya Akahoshi Fumiaki Takenaka Takahisa Hanada Masaru Akehi Takanori Sasaki Ken-ei Sada Eiji Matsuura Masahiro Nishibori Jun Wada |
| author_sort | Haruki Watanabe |
| collection | DOAJ |
| description | We evaluated the efficacy of a neutralizing anti-high mobility group box 1 (HMGB1) monoclonal antibody in MRL/lpr lupus-prone mice. The anti-HMGB1 monoclonal antibody (5 mg/kg weight) or class-matched control immunoglobulin G2a (IgG2a) was administered intravenously twice a week for 4–15 weeks. Urine albumin was monitored, and histological evaluation of the kidneys was conducted at 16 weeks. Lymphadenopathies were evaluated by 1-(2′-deoxy-2′-[18F]fluoro-β-D-arabinofuranosyl)cytosine ([18F]FAC) positron emission tomography/computed tomography (PET/CT) at 12 weeks. Following 4-week treatment, [18F]FAC-PET/CT showed similar accumulation in cervical and axillary lymph nodes at 12 weeks of age. However, anti-HMGB1 monoclonal antibody sufficiently inhibited the increase in albuminuria compared to an isotype control following 15-week treatment. Complement deposition was also improved; however, there were no significant differences in IgG deposition and renal pathological scores between the two groups. Anti-double-stranded DNA (dsDNA) antibody titers and cytokine and chemokine levels were also unaltered. Although there were no significant differences in glomerular macrophage infiltration, neutrophil infiltration was significantly decreased by the anti-HMGB1 monoclonal antibody. Antagonizing HMGB1 treatment suppressed HMGB1 translocation from nuclei in the kidney and suppressed neutrophil extracellular traps. The anti-HMGB1 monoclonal antibody demonstrated therapeutic potential against albuminuria in lupus nephritis by inhibiting neutrophil recruitment and neutrophil extracellular traps. |
| first_indexed | 2024-12-22T09:07:56Z |
| format | Article |
| id | doaj.art-d9c450937db040a6a6176851feff171f |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-22T09:07:56Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-d9c450937db040a6a6176851feff171f2022-12-21T18:31:33ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012017-09-016C313910.1016/j.omtm.2017.05.006Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone MiceHaruki Watanabe0Katsue S. Watanabe1Keyue Liu2Sumie Hiramatsu3Sonia Zeggar4Eri Katsuyama5Noriko Tatebe6Akiya Akahoshi7Fumiaki Takenaka8Takahisa Hanada9Masaru Akehi10Takanori Sasaki11Ken-ei Sada12Eiji Matsuura13Masahiro Nishibori14Jun Wada15Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanCollaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, JapanCollaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, JapanCollaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, JapanCollaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, JapanCollaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanCollaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanWe evaluated the efficacy of a neutralizing anti-high mobility group box 1 (HMGB1) monoclonal antibody in MRL/lpr lupus-prone mice. The anti-HMGB1 monoclonal antibody (5 mg/kg weight) or class-matched control immunoglobulin G2a (IgG2a) was administered intravenously twice a week for 4–15 weeks. Urine albumin was monitored, and histological evaluation of the kidneys was conducted at 16 weeks. Lymphadenopathies were evaluated by 1-(2′-deoxy-2′-[18F]fluoro-β-D-arabinofuranosyl)cytosine ([18F]FAC) positron emission tomography/computed tomography (PET/CT) at 12 weeks. Following 4-week treatment, [18F]FAC-PET/CT showed similar accumulation in cervical and axillary lymph nodes at 12 weeks of age. However, anti-HMGB1 monoclonal antibody sufficiently inhibited the increase in albuminuria compared to an isotype control following 15-week treatment. Complement deposition was also improved; however, there were no significant differences in IgG deposition and renal pathological scores between the two groups. Anti-double-stranded DNA (dsDNA) antibody titers and cytokine and chemokine levels were also unaltered. Although there were no significant differences in glomerular macrophage infiltration, neutrophil infiltration was significantly decreased by the anti-HMGB1 monoclonal antibody. Antagonizing HMGB1 treatment suppressed HMGB1 translocation from nuclei in the kidney and suppressed neutrophil extracellular traps. The anti-HMGB1 monoclonal antibody demonstrated therapeutic potential against albuminuria in lupus nephritis by inhibiting neutrophil recruitment and neutrophil extracellular traps.http://www.sciencedirect.com/science/article/pii/S2329050117300712high mobility group box 1lupus nephritissystemic lupus erythematosusalbuminurianeutrophil extracellular traps |
| spellingShingle | Haruki Watanabe Katsue S. Watanabe Keyue Liu Sumie Hiramatsu Sonia Zeggar Eri Katsuyama Noriko Tatebe Akiya Akahoshi Fumiaki Takenaka Takahisa Hanada Masaru Akehi Takanori Sasaki Ken-ei Sada Eiji Matsuura Masahiro Nishibori Jun Wada Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice Molecular Therapy: Methods & Clinical Development high mobility group box 1 lupus nephritis systemic lupus erythematosus albuminuria neutrophil extracellular traps |
| title | Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice |
| title_full | Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice |
| title_fullStr | Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice |
| title_full_unstemmed | Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice |
| title_short | Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice |
| title_sort | anti high mobility group box 1 antibody ameliorates albuminuria in mrl lpr lupus prone mice |
| topic | high mobility group box 1 lupus nephritis systemic lupus erythematosus albuminuria neutrophil extracellular traps |
| url | http://www.sciencedirect.com/science/article/pii/S2329050117300712 |
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