Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease
© 2022. The Author(s)..
BACKGROUND: Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, "VasSF," based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj). Apolipoprotein A-2 (ApoA2) has been identified as one of VasSF's target molecules.
METHODS: Here, we tested the potential of anti-apolipoprotein A-2 antibodies (anti-ApoA2) as a new therapeutic drug against KD by examining its effect on a mouse model, in which KD was induced via Candida albicans water-soluble fraction (CAWS). CAWS (2 mg/mouse) was injected intraperitoneally into C57BL/6NCrSlc mice for five consecutive days. The incidence and histological severity of vasculitis in CAWS-induced coronary arteritis in mice administered anti-ApoA2 was examined. The following experimental groups were tested: solvent (only PBS (-) injection); anti-ApoA2 antibodies at dosages of 0.05 mg, 0.1 mg, and 0.5 mg/kg/day; human IgG at 0.1 mg/kg/day.
RESULTS: The group treated with anti-ApoA2 0.5 mg/kg/day showed a lower incidence of panvasculitis induced by CAWS, less inflammation of the coronary arteries and aortic roots, and lower levels of serum IL-6, M-CSF, and MIP-1α and 32 cytokines/chemokines compared with those in the solvent group.
CONCLUSIONS: The anti-ApoA2 treatment suppressed the development of coronary arteritis in an animal KD model and anti-ApoA2 shows potential as an effective therapeutic candidate for the treatment of KD vasculitis. The use of specific antibodies that display higher vasculitis-suppressing effects, such as anti-ApoA2, may attenuate KD as well as other infectious diseases, with less severe adverse side effects than treatment with IVIg.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Pediatric rheumatology online journal - 20(2022), 1 vom: 22. Dez., Seite 119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ito, Fuyu [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-apolipoprotein A-2 |
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| Anmerkungen: |
Date Completed 26.12.2022 Date Revised 26.12.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12969-022-00783-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350619956 |
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| 245 | 1 | 0 | |a Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 26.12.2022 | ||
| 500 | |a Date Revised 26.12.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a BACKGROUND: Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, "VasSF," based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj). Apolipoprotein A-2 (ApoA2) has been identified as one of VasSF's target molecules | ||
| 520 | |a METHODS: Here, we tested the potential of anti-apolipoprotein A-2 antibodies (anti-ApoA2) as a new therapeutic drug against KD by examining its effect on a mouse model, in which KD was induced via Candida albicans water-soluble fraction (CAWS). CAWS (2 mg/mouse) was injected intraperitoneally into C57BL/6NCrSlc mice for five consecutive days. The incidence and histological severity of vasculitis in CAWS-induced coronary arteritis in mice administered anti-ApoA2 was examined. The following experimental groups were tested: solvent (only PBS (-) injection); anti-ApoA2 antibodies at dosages of 0.05 mg, 0.1 mg, and 0.5 mg/kg/day; human IgG at 0.1 mg/kg/day | ||
| 520 | |a RESULTS: The group treated with anti-ApoA2 0.5 mg/kg/day showed a lower incidence of panvasculitis induced by CAWS, less inflammation of the coronary arteries and aortic roots, and lower levels of serum IL-6, M-CSF, and MIP-1α and 32 cytokines/chemokines compared with those in the solvent group | ||
| 520 | |a CONCLUSIONS: The anti-ApoA2 treatment suppressed the development of coronary arteritis in an animal KD model and anti-ApoA2 shows potential as an effective therapeutic candidate for the treatment of KD vasculitis. The use of specific antibodies that display higher vasculitis-suppressing effects, such as anti-ApoA2, may attenuate KD as well as other infectious diseases, with less severe adverse side effects than treatment with IVIg | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anti-apolipoprotein A-2 | |
| 650 | 4 | |a Coronary arteritis | |
| 650 | 4 | |a Kawasaki disease | |
| 650 | 4 | |a Vasculitis | |
| 650 | 7 | |a Immunoglobulins, Intravenous |2 NLM | |
| 650 | 7 | |a Solvents |2 NLM | |
| 700 | 1 | |a Oharaseki, Toshiaki |e verfasserin |4 aut | |
| 700 | 1 | |a Tsukui, Daisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Kimura, Yoshitaka |e verfasserin |4 aut | |
| 700 | 1 | |a Yanagida, Tamiko |e verfasserin |4 aut | |
| 700 | 1 | |a Kishi, Fukuko |e verfasserin |4 aut | |
| 700 | 1 | |a Yamakawa, Yoshio |e verfasserin |4 aut | |
| 700 | 1 | |a Kameoka, Yosuke |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Shoichi |e verfasserin |4 aut | |
| 700 | 1 | |a Uno, Kazuko |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Osamu |e verfasserin |4 aut | |
| 700 | 1 | |a Miura, Noriko N |e verfasserin |4 aut | |
| 700 | 1 | |a Ohno, Naohito |e verfasserin |4 aut | |
| 700 | 1 | |a Takahashi, Kei |e verfasserin |4 aut | |
| 700 | 1 | |a Kono, Hajime |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Kazuo |e verfasserin |4 aut | |
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