Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus

• Published in: Arthritis research & therapy Vol. 25; no. 1; p. 76
• Main Authors: Kitagori, Koji, Oku, Takuma, Wakabayashi, Masaki, Nakajima, Tomoya, Nakashima, Ran, Murakami, Kosaku, Hirayama, Yoshitaka, Ishihama, Yasushi, Ohmura, Koichiro, Morinobu, Akio, Mimori, Tsuneyo, Yoshifuji, Hajime
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.05.2023; BioMed Central; BMC
• Subjects: Analysis; Antibodies; Arthritis; Autoantibodies; B cells; B-Lymphocytes - metabolism; Calgranulin A - genetics; Care and treatment; Chromatography; Cloning; Corticosteroids; Datasets; Dendritic cells; Diagnosis; Disease; DNA microarrays; Dosage and administration; Enzymes; FDA approval; Flow cytometry; Gene expression; Genomics; Humans; Immunoassay; Immunotherapy; Liquid chromatography; Lupus; Lupus Erythematosus, Systemic; Mass spectrometry; Monocytes - metabolism; Multiple sclerosis; Pathophysiology; Patient outcomes; Patients; Peptides; Physiology, Pathological; Proteins; Proteomics; RNA, Messenger - metabolism; S100A8; Scientific imaging; Systemic lupus erythematosus; Testing; Japan; Canada; United States > US; Switzerland; S100A8; Systemic lupus erythematosus; B cells
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-023-03057-z

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. 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. 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. 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.