Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes
Abstract Background Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which dysregulation of B cells has been recognized. Here, we searched for potential biomarkers of SLE using liquid chromatography-tandem mass spectrometry (LC-MS). Methods Lymph nodes from SLE patients and...
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doaj-aeda6bee64244496932d464a1ae2f5562020-11-24T22:12:28ZengBMCArthritis Research & Therapy1478-63622018-01-0120111110.1186/s13075-018-1511-5Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodesAya Miyagawa-Hayashino0Hajime Yoshifuji1Koji Kitagori2Shinji Ito3Takuma Oku4Yoshitaka Hirayama5Adeeb Salah6Toshiki Nakajima7Kaori Kiso8Norishige Yamada9Hironori Haga10Tatsuaki Tsuruyama11Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityCenter for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto UniversityBio Frontier Platform, Graduate School of Medicine, Kyoto UniversityCenter for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto UniversityCenter for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto UniversityDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityCenter for Anatomical, Pathological and Forensic Medical Research, Graduate School of Medicine, Kyoto UniversityCenter for Anatomical, Pathological and Forensic Medical Research, Graduate School of Medicine, Kyoto UniversityDepartment of Diagnostic Pathology, Kyoto University HospitalCenter for Anatomical, Pathological and Forensic Medical Research, Graduate School of Medicine, Kyoto UniversityAbstract Background Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which dysregulation of B cells has been recognized. Here, we searched for potential biomarkers of SLE using liquid chromatography-tandem mass spectrometry (LC-MS). Methods Lymph nodes from SLE patients and controls were analyzed by LC-MS. To validate the identified molecules, immunoblotting and immunohistochemistry were performed and B cells from SLE patients were analyzed by quantitative RT-PCR. B-cell subsets from NZB/W F1 mice, which exhibit autoimmune disease resembling human SLE, were analyzed by flow cytometry. Endoplasmic reticulum (ER) stress was induced by tunicamycin and the serum concentration of anti-dsDNA antibodies was determined by ELISA. TUNEL methods and immunoblotting were used to assess the effect of tunicamycin. Results MZB1, which comprises part of a B-cell-specific ER chaperone complex and is a key player in antibody secretion, was one of the differentially expressed proteins identified by LC-MS and confirmed by immunoblotting. Immunohistochemically, larger numbers of MZB1+ cells were located mainly in interfollicular areas and scattered in germinal centers in specimens from SLE patients compared with those from controls. MZB1 colocalized with CD138+ plasma cells and IRTA1+ marginal zone B cells. MZB1 mRNA was increased by 2.1-fold in B cells of SLE patients with active disease (SLE Disease Activity Index 2000 ≥ 6) compared with controls. In aged NZB/W F1 mice, splenic marginal zone B cells and plasma cells showed elevated MZB1 levels. Tunicamycin induced apoptosis of MZB1+ cells in target organs, resulting in decreased serum anti-dsDNA antibody levels. Additionally, MZB1+ cells were increased in synovial tissue specimens from patients with rheumatoid arthritis. Conclusions MZB1 may be a potential therapeutic target in excessive antibody-secreting cells in SLE.http://link.springer.com/article/10.1186/s13075-018-1511-5Formalin-fixed paraffin-embeddedLupus-prone miceProteomic analysisSystemic lupus erythematosusSLE lymphadenopathyTUNEL |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aya Miyagawa-Hayashino Hajime Yoshifuji Koji Kitagori Shinji Ito Takuma Oku Yoshitaka Hirayama Adeeb Salah Toshiki Nakajima Kaori Kiso Norishige Yamada Hironori Haga Tatsuaki Tsuruyama |
spellingShingle |
Aya Miyagawa-Hayashino Hajime Yoshifuji Koji Kitagori Shinji Ito Takuma Oku Yoshitaka Hirayama Adeeb Salah Toshiki Nakajima Kaori Kiso Norishige Yamada Hironori Haga Tatsuaki Tsuruyama Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes Arthritis Research & Therapy Formalin-fixed paraffin-embedded Lupus-prone mice Proteomic analysis Systemic lupus erythematosus SLE lymphadenopathy TUNEL |
author_facet |
Aya Miyagawa-Hayashino Hajime Yoshifuji Koji Kitagori Shinji Ito Takuma Oku Yoshitaka Hirayama Adeeb Salah Toshiki Nakajima Kaori Kiso Norishige Yamada Hironori Haga Tatsuaki Tsuruyama |
author_sort |
Aya Miyagawa-Hayashino |
title |
Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes |
title_short |
Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes |
title_full |
Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes |
title_fullStr |
Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes |
title_full_unstemmed |
Increase of MZB1 in B cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes |
title_sort |
increase of mzb1 in b cells in systemic lupus erythematosus: proteomic analysis of biopsied lymph nodes |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2018-01-01 |
description |
Abstract Background Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which dysregulation of B cells has been recognized. Here, we searched for potential biomarkers of SLE using liquid chromatography-tandem mass spectrometry (LC-MS). Methods Lymph nodes from SLE patients and controls were analyzed by LC-MS. To validate the identified molecules, immunoblotting and immunohistochemistry were performed and B cells from SLE patients were analyzed by quantitative RT-PCR. B-cell subsets from NZB/W F1 mice, which exhibit autoimmune disease resembling human SLE, were analyzed by flow cytometry. Endoplasmic reticulum (ER) stress was induced by tunicamycin and the serum concentration of anti-dsDNA antibodies was determined by ELISA. TUNEL methods and immunoblotting were used to assess the effect of tunicamycin. Results MZB1, which comprises part of a B-cell-specific ER chaperone complex and is a key player in antibody secretion, was one of the differentially expressed proteins identified by LC-MS and confirmed by immunoblotting. Immunohistochemically, larger numbers of MZB1+ cells were located mainly in interfollicular areas and scattered in germinal centers in specimens from SLE patients compared with those from controls. MZB1 colocalized with CD138+ plasma cells and IRTA1+ marginal zone B cells. MZB1 mRNA was increased by 2.1-fold in B cells of SLE patients with active disease (SLE Disease Activity Index 2000 ≥ 6) compared with controls. In aged NZB/W F1 mice, splenic marginal zone B cells and plasma cells showed elevated MZB1 levels. Tunicamycin induced apoptosis of MZB1+ cells in target organs, resulting in decreased serum anti-dsDNA antibody levels. Additionally, MZB1+ cells were increased in synovial tissue specimens from patients with rheumatoid arthritis. Conclusions MZB1 may be a potential therapeutic target in excessive antibody-secreting cells in SLE. |
topic |
Formalin-fixed paraffin-embedded Lupus-prone mice Proteomic analysis Systemic lupus erythematosus SLE lymphadenopathy TUNEL |
url |
http://link.springer.com/article/10.1186/s13075-018-1511-5 |
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