Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice

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, Kenei Sada, Eiji Matsuura, Masahiro Nishibori, Jun Wada

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)31-39
Number of pages9
JournalMolecular Therapy - Methods and Clinical Development
Volume6
DOIs
Publication statusPublished - Sep 15 2017

Fingerprint

Albuminuria
Monoclonal Antibodies
Antibodies
Neutrophil Infiltration
Kidney
Lupus Nephritis
Chemokines
Immunoglobulins
Albumins
Immunoglobulin G
Lymph Nodes
Macrophages
Urine
Cytokines
Weights and Measures

Keywords

  • albuminuria
  • high mobility group box 1
  • lupus nephritis
  • neutrophil extracellular traps
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine

Cite this

Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice. / Watanabe, Haruki; Watanabe, Katsue S.; Liu, Keyue; Hiramatsu, Sumie; Zeggar, Sonia; Katsuyama, Eri; Tatebe, Noriko; Akahoshi, Akiya; Takenaka, Fumiaki; Hanada, Takahisa; Akehi, Masaru; Sasaki, Takanori; Sada, Kenei; Matsuura, Eiji; Nishibori, Masahiro; Wada, Jun.

In: Molecular Therapy - Methods and Clinical Development, Vol. 6, 15.09.2017, p. 31-39.

Research output: Contribution to journalArticle

@article{31a89bd5c6ee43a2b4a785bfe23697ac,
title = "Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice",
abstract = "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.",
keywords = "albuminuria, high mobility group box 1, lupus nephritis, neutrophil extracellular traps, systemic lupus erythematosus",
author = "Haruki Watanabe and Watanabe, {Katsue S.} and Keyue Liu and Sumie Hiramatsu and Sonia Zeggar and Eri Katsuyama and Noriko Tatebe and Akiya Akahoshi and Fumiaki Takenaka and Takahisa Hanada and Masaru Akehi and Takanori Sasaki and Kenei Sada and Eiji Matsuura and Masahiro Nishibori and Jun Wada",
year = "2017",
month = "9",
day = "15",
doi = "10.1016/j.omtm.2017.05.006",
language = "English",
volume = "6",
pages = "31--39",
journal = "Molecular Therapy - Methods and Clinical Development",
issn = "2329-0501",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice

AU - Watanabe, Haruki

AU - Watanabe, Katsue S.

AU - Liu, Keyue

AU - Hiramatsu, Sumie

AU - Zeggar, Sonia

AU - Katsuyama, Eri

AU - Tatebe, Noriko

AU - Akahoshi, Akiya

AU - Takenaka, Fumiaki

AU - Hanada, Takahisa

AU - Akehi, Masaru

AU - Sasaki, Takanori

AU - Sada, Kenei

AU - Matsuura, Eiji

AU - Nishibori, Masahiro

AU - Wada, Jun

PY - 2017/9/15

Y1 - 2017/9/15

N2 - 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.

AB - 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.

KW - albuminuria

KW - high mobility group box 1

KW - lupus nephritis

KW - neutrophil extracellular traps

KW - systemic lupus erythematosus

UR - http://www.scopus.com/inward/record.url?scp=85029309701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029309701&partnerID=8YFLogxK

U2 - 10.1016/j.omtm.2017.05.006

DO - 10.1016/j.omtm.2017.05.006

M3 - Article

VL - 6

SP - 31

EP - 39

JO - Molecular Therapy - Methods and Clinical Development

JF - Molecular Therapy - Methods and Clinical Development

SN - 2329-0501

ER -