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Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease

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...

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Autores principales: Ito, Fuyu, Oharaseki, Toshiaki, Tsukui, Daisuke, Kimura, Yoshitaka, Yanagida, Tamiko, Kishi, Fukuko, Yamakawa, Yoshio, Kameoka, Yosuke, Suzuki, Shoichi, Uno, Kazuko, Suzuki, Osamu, Miura, Noriko N., Ohno, Naohito, Takahashi, Kei, Kono, Hajime, Suzuki, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773535/
https://www.ncbi.nlm.nih.gov/pubmed/36550471
http://dx.doi.org/10.1186/s12969-022-00783-7
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author Ito, Fuyu
Oharaseki, Toshiaki
Tsukui, Daisuke
Kimura, Yoshitaka
Yanagida, Tamiko
Kishi, Fukuko
Yamakawa, Yoshio
Kameoka, Yosuke
Suzuki, Shoichi
Uno, Kazuko
Suzuki, Osamu
Miura, Noriko N.
Ohno, Naohito
Takahashi, Kei
Kono, Hajime
Suzuki, Kazuo
author_facet Ito, Fuyu
Oharaseki, Toshiaki
Tsukui, Daisuke
Kimura, Yoshitaka
Yanagida, Tamiko
Kishi, Fukuko
Yamakawa, Yoshio
Kameoka, Yosuke
Suzuki, Shoichi
Uno, Kazuko
Suzuki, Osamu
Miura, Noriko N.
Ohno, Naohito
Takahashi, Kei
Kono, Hajime
Suzuki, Kazuo
author_sort Ito, Fuyu
collection PubMed
description 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.
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spelling pubmed-97735352022-12-22 Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease Ito, Fuyu Oharaseki, Toshiaki Tsukui, Daisuke Kimura, Yoshitaka Yanagida, Tamiko Kishi, Fukuko Yamakawa, Yoshio Kameoka, Yosuke Suzuki, Shoichi Uno, Kazuko Suzuki, Osamu Miura, Noriko N. Ohno, Naohito Takahashi, Kei Kono, Hajime Suzuki, Kazuo Pediatr Rheumatol Online J Research Article 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. BioMed Central 2022-12-22 /pmc/articles/PMC9773535/ /pubmed/36550471 http://dx.doi.org/10.1186/s12969-022-00783-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Ito, Fuyu
Oharaseki, Toshiaki
Tsukui, Daisuke
Kimura, Yoshitaka
Yanagida, Tamiko
Kishi, Fukuko
Yamakawa, Yoshio
Kameoka, Yosuke
Suzuki, Shoichi
Uno, Kazuko
Suzuki, Osamu
Miura, Noriko N.
Ohno, Naohito
Takahashi, Kei
Kono, Hajime
Suzuki, Kazuo
Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease
title Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease
title_full Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease
title_fullStr Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease
title_full_unstemmed Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease
title_short Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease
title_sort beneficial effects of anti-apolipoprotein a-2 on an animal model for coronary arteritis in kawasaki disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773535/
https://www.ncbi.nlm.nih.gov/pubmed/36550471
http://dx.doi.org/10.1186/s12969-022-00783-7
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