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Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus
BACKGROUND: Systemic lupus erythematosus (SLE) is an intractable disease characterized by autoantibody production and autoreactive B and T cell proliferation. Although several studies have revealed multiple genetic and environmental associations, the underlying mechanisms remain unknown. METHODS: We...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170829/ https://www.ncbi.nlm.nih.gov/pubmed/37165399 http://dx.doi.org/10.1186/s13075-023-03057-z |
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author | Kitagori, Koji Oku, Takuma Wakabayashi, Masaki Nakajima, Tomoya Nakashima, Ran Murakami, Kosaku Hirayama, Yoshitaka Ishihama, Yasushi Ohmura, Koichiro Morinobu, Akio Mimori, Tsuneyo Yoshifuji, Hajime |
author_facet | Kitagori, Koji Oku, Takuma Wakabayashi, Masaki Nakajima, Tomoya Nakashima, Ran Murakami, Kosaku Hirayama, Yoshitaka Ishihama, Yasushi Ohmura, Koichiro Morinobu, Akio Mimori, Tsuneyo Yoshifuji, Hajime |
author_sort | Kitagori, Koji |
collection | PubMed |
description | BACKGROUND: Systemic lupus erythematosus (SLE) is an intractable disease characterized by autoantibody production and autoreactive B and T cell proliferation. Although several studies have revealed multiple genetic and environmental associations, the underlying mechanisms remain unknown. METHODS: We performed proteomics and transcriptomics using liquid chromatography-mass spectrometry and DNA microarray, using peripheral blood B cells from patients with SLE, and healthy controls (HC). We explored molecules associated with the pathophysiology of SLE by flow cytometry and B cell stimulation assay. RESULTS: We identified for the first time that expression of both S100A8 protein and mRNA were markedly upregulated in SLE B cells. The results obtained using flow cytometry showed that S100A8 was highly expressed on the surface of B cells of patients with active SLE (MFI; HC 102.5 ± 5.97, stable SLE 111.4 ± 12.87, active SLE 586.9 ± 142.9), and S100A8 on the cell surface was decreased after treatment (MFI; pre-treat 1094.5 ± 355.38, post-treat 492.25 ± 247.39); therefore, it is suggested that S100A8 may be a marker for disease activity. The mRNA expression of S100A8 was particularly upregulated in memory B cells of SLE (56.68 fold higher than HC), suggesting that S100A8 may be mainly secreted by memory B cells in the pathogenesis of SLE. CONCLUSIONS: Our results imply that the S100A8 proteins secreted from memory B cells may stimulate granulocytes and monocytes through pattern recognition receptors, activate the innate immune system, and are involved in the pathogenesis of SLE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-023-03057-z. |
format | Online Article Text |
id | pubmed-10170829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101708292023-05-11 Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus Kitagori, Koji Oku, Takuma Wakabayashi, Masaki Nakajima, Tomoya Nakashima, Ran Murakami, Kosaku Hirayama, Yoshitaka Ishihama, Yasushi Ohmura, Koichiro Morinobu, Akio Mimori, Tsuneyo Yoshifuji, Hajime Arthritis Res Ther Research BACKGROUND: Systemic lupus erythematosus (SLE) is an intractable disease characterized by autoantibody production and autoreactive B and T cell proliferation. Although several studies have revealed multiple genetic and environmental associations, the underlying mechanisms remain unknown. METHODS: We performed proteomics and transcriptomics using liquid chromatography-mass spectrometry and DNA microarray, using peripheral blood B cells from patients with SLE, and healthy controls (HC). We explored molecules associated with the pathophysiology of SLE by flow cytometry and B cell stimulation assay. RESULTS: We identified for the first time that expression of both S100A8 protein and mRNA were markedly upregulated in SLE B cells. The results obtained using flow cytometry showed that S100A8 was highly expressed on the surface of B cells of patients with active SLE (MFI; HC 102.5 ± 5.97, stable SLE 111.4 ± 12.87, active SLE 586.9 ± 142.9), and S100A8 on the cell surface was decreased after treatment (MFI; pre-treat 1094.5 ± 355.38, post-treat 492.25 ± 247.39); therefore, it is suggested that S100A8 may be a marker for disease activity. The mRNA expression of S100A8 was particularly upregulated in memory B cells of SLE (56.68 fold higher than HC), suggesting that S100A8 may be mainly secreted by memory B cells in the pathogenesis of SLE. CONCLUSIONS: Our results imply that the S100A8 proteins secreted from memory B cells may stimulate granulocytes and monocytes through pattern recognition receptors, activate the innate immune system, and are involved in the pathogenesis of SLE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-023-03057-z. BioMed Central 2023-05-10 2023 /pmc/articles/PMC10170829/ /pubmed/37165399 http://dx.doi.org/10.1186/s13075-023-03057-z Text en © The Author(s) 2023 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 Kitagori, Koji Oku, Takuma Wakabayashi, Masaki Nakajima, Tomoya Nakashima, Ran Murakami, Kosaku Hirayama, Yoshitaka Ishihama, Yasushi Ohmura, Koichiro Morinobu, Akio Mimori, Tsuneyo Yoshifuji, Hajime Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus |
title | Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus |
title_full | Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus |
title_fullStr | Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus |
title_full_unstemmed | Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus |
title_short | Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus |
title_sort | expression of s100a8 protein on b cells is associated with disease activity in patients with systemic lupus erythematosus |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170829/ https://www.ncbi.nlm.nih.gov/pubmed/37165399 http://dx.doi.org/10.1186/s13075-023-03057-z |
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