Review
Biochemistry & Molecular Biology
Helena Idborg, Vilija Oke
Summary: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by activation and dysregulation of the immune system. Disturbances in immune pathways and genetic susceptibility are key factors in the development of SLE. Dysregulation of cytokines, particularly interferons, has been extensively studied as potential biomarkers and treatment targets in SLE.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Shingo Nakayamada, Yoshiya Tanaka
Summary: The treatment of rheumatoid arthritis was revolutionized with the use of molecular-targeted drugs that target immunoregulatory molecules. The success of treatment with these drugs prompted the development of molecular-targeted drugs for systemic lupus erythematosus. However, systemic lupus erythematosus is a disease with high heterogeneous immune abnormalities, and diverse cells or molecules can be treatment targets. Thus, the identification of subpopulations based on immune abnormalities is essential for the development of effective treatment.
Article
Immunology
Xiaolan Huang, Laurence Don Wai Luu, Nan Jia, Jia Zhu, Jin Fu, Fei Xiao, Chunyan Liu, Shengnan Li, Gaixiu Shu, Jun Hou, Min Kang, Dan Zhang, Yingjie Xu, Yi Wang, Xiaodai Cui, Jianming Lai, Jieqiong Li, Jun Tai
Summary: This study investigated the molecular characteristics of systemic lupus erythematosus (SLE) patients with different disease activity levels using a comprehensive multi-omics analysis. The results showed that the complement system and inflammatory response were activated in SLE patients and were associated with disease activity. Additionally, the immunoglobulin mediated immune response was activated in patients with low disease activity but slightly suppressed in patients with high disease activity. Imbalance in lipid metabolism, particularly sphingolipid metabolism, and dysregulated apolipoproteins were also observed to contribute to the disease activity of SLE.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
James Greenan-Barrett, Georgia Doolan, Devina Shah, Simrun Virdee, George A. Robinson, Varvara Choida, Nataliya Gak, Nina de Gruijter, Elizabeth Rosser, Muthana Al-Obaidi, Maria Leandro, Michael S. Zandi, Ruth J. Pepper, Alan Salama, Elizabeth C. Jury, Coziana Ciurtin
Summary: Juvenile systemic lupus erythematosus (JSLE) is a form of lupus that occurs before 18 years of age and is associated with more severe disease phenotype, increased morbidity, and mortality compared to adult-onset SLE. Identifying biomarkers specific to JSLE clinical phenotype can lead to better patient management and outcomes. Research into various traditional and novel biomarkers is important for predicting organ involvement and improving treatment strategies for JSLE.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Ji-Won Kim, Ju-Yang Jung, Sang-Won Lee, Wook-Young Baek, Hyoun-Ah Kim, Chang-Hee Suh
Summary: This study demonstrates that the expression of S100A8 in serum, urine, and saliva is significantly higher in patients with SLE than in healthy controls and is correlated with disease activity markers. Therefore, S100A8 protein could be a potential biomarker for SLE.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Dominika Blachut, Brygida Przywara-Chowaniec, Andrzej Tomasik, Tomasz Kukulski, Beata Morawiec
Summary: Systemic lupus erythematosus is associated with an increased risk of premature atherosclerosis. This review focuses on biomarkers of atherosclerosis in SLE, particularly immune markers. Chronic inflammation of the vascular wall is a significant cause of cardiovascular disease events.
Article
Microbiology
Ping Yang, Rui Xu, Fei Chen, Shanshan Chen, Adeel Khan, Liang Li, Xiaoshan Zhang, Yanbo Wang, Zhipeng Xu, Han Shen
Summary: This study investigates the gut fungal dysbiosis and ecology in patients with SLE and demonstrates the applicability of fungal species as diagnostic tools for SLE. It suggests that the interaction between the gut fungal mycobiome and the host may contribute to the pathogenesis of the disease.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Immunology
Mengmeng Xiang, Yilun Wang, Zhanyan Gao, Jie Wang, Qian Chen, Zhan Sun, Jun Liang, Jinhua Xu
Summary: This study used Mendelian randomization to assess the causal correlations between 41 inflammatory cytokines and systemic lupus erythematosus (SLE). The results suggested that CTACK and IL-17 may be associated with the risk of SLE, while several other inflammatory cytokines may be consequences of SLE development.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medical Laboratory Technology
Jian-Jun Huang, Tong-Jun Mao, Zi-Yu Zhang, Gang Feng
Summary: The study investigates the role of lymphocyte-bound C4d and immunoglobulins in the diagnosis and monitoring of SLE. The levels of C4d and Igs were measured in SLE patients, patients with other inflammatory diseases, and healthy individuals. The results suggest that LB-C4d/Igs could be used as reliable indicators for SLE diagnosis and activity monitoring.
CLINICAL BIOCHEMISTRY
(2023)
Review
Clinical Neurology
Jonathan S. Emerson, Simon M. Gruenewald, Lavier Gomes, Ming-Wei Lin, Sanjay Swaminathan
Summary: Recognizing neuropsychiatric involvement by SLE is essential but currently available diagnostic algorithms have many barriers that may delay diagnosis and treatment. The non-specific symptoms, markers, and neuroimaging findings of NPSLE highlight research gaps. Neuropsychological assessments and novel markers show promise in improving recognition. A composite panel of investigations may be needed to address the recognition gaps.
FRONTIERS IN NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Konstantinos Parperis, Nikolaos Velidakis, Elina Khattab, Evangelia Gkougkoudi, Nikolaos P. E. Kadoglou
Summary: Pulmonary hypertension is commonly seen in patients with systemic lupus erythematosus, presenting with non-specific symptoms and negatively affecting survival. It can result from immune system dysregulation, as well as various other conditions. Early diagnosis and identification of underlying pathogenetic mechanisms are crucial for introducing targeted therapy and preventing irreversible pulmonary vascular damage. The management of pulmonary hypertension in SLE patients is similar to that of idiopathic PAH, but specific diagnostic tools for early diagnosis seem to be unavailable yet.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Environmental
Ting Liu, Xi Zhang, Lizhen He, Zehang Zhang, Yuhan Sun, Junmei Feng, Zhiming Lin, Tianfeng Chen
Summary: This study developed a selenium nanosystem with surface decoration of calf thymus DNA to specifically recognize and remove anti-dsDNA autoantibodies in SLE patients. The nanotherapeutics showed excellent biocompatibility and safety, and had higher clearance ratio compared to other clinical products. Furthermore, the nanotherapeutics could visualize the distribution of anti-dsDNA antibodies in kidney lesions and semi-quantify the antibody deposition.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Immunology
Shan Song, Jing-Yuan Zhang, Fang-Yue Liu, He-Yi Zhang, Xiao-Feng Li, Sheng-Xiao Zhang
Summary: This study identified hub genes and key pathways associated with naive and memory B cells, providing novel insights into the behavior of B cells and the pathogenesis of SLE.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Immunology
Gabriela Guzman-Martinez, Concepcion Maranon
Summary: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD), which is becoming one of the most relevant complications and a significant factor causing morbidity and mortality in SLE. Immune constituents, including specific circulating cell populations, autoantibodies, and inflammatory mediators, play a role in the pathogenesis of atherosclerosis and endothelial damage in SLE patients. This review summarizes the presentation of CVD in SLE, the role of autoimmune responses in inducing atherogenesis, endothelial impairment, and cardiac disease, and discusses the utility of immune mediators as early CVD biomarkers and targets for clinical intervention in SLE patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Julius Lindblom, Daniel Toro-Dominguez, Elena Carnero-Montoro, Lorenzo Beretta, Maria Orietta Borghi, Jessica Castillo, Yvonne Enman, Chandra Mohan, Marta E. Alarcon-Riquelme, Guillermo Barturen, Ioannis Parodis
Summary: This study aimed to investigate the transcriptome, eQTLs, and serological markers in SLE patients compared to healthy controls. The analysis revealed the significance of interferon signaling pathways and downregulation of lymphocyte signaling cluster in renal activity. Upregulation of interferon-related genes indicated hematological activity and vasculitis. Modulation of interferon, STAT1, PLK1, B and plasma cell signatures showed promise as viable approaches to treat SLE.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Allergy
Hideyuki Takahashi, Toshihiko Komai, Keigo Setoguchi, Hirofumi Shoda, Keishi Fujio
Summary: This study proposed a scoring system to differentiate eosinophilic granulomatosis with polyangiitis (EGPA) from other eosinophilic disorders. Through unsupervised hierarchical clustering and principal component analysis, two distinct clusters were identified among 58 patients with eosinophilia-related diseases. Based on these features, a 16-point scoring system was established and validated in a separate cohort.
ALLERGOLOGY INTERNATIONAL
(2023)
Article
Immunology
Kazuki M. Matsuda, Hirohito Kotani, Kei Yamaguchi, Taishi Okumura, Eriko Fukuda, Masanori Kono, Teruyoshi Hisamoto, Ruriko Kawanabe, Yuta Norimatsu, Ai Kuzumi, Maiko Fukayama, Takemichi Fukasawa, Satoshi Ebata, Asako Yoshizaki-Ogawa, Tomohisa Okamura, Hirofumi Shoda, Keishi Fujio, Naoki Goshima, Shinichi Sato, Ayumi Yoshizaki
Summary: Cutaneous arteritis (CA) is a skin vasculitis that affects small to medium-sized arteries. The diagnosis relies on skin biopsy, which can be burdensome. The pathogenesis and treatment of CA are still unclear. In this study, anti-transcobalamin receptor (TCblR) antibodies were found in 24% of CA patients and were associated with skin-limited CA. These antibodies trigger interleukin-6 autocrine loop and induce periarterial inflammation. Methylcobalamin, a ligand of TCblR, can ameliorate inflammation caused by these antibodies. These findings suggest that anti-TCblR antibodies could be a diagnostic marker and a therapeutic target for CA.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Rheumatology
Saeko Yamada, Yasuo Nagafuchi, Min Wang, Mineto Ota, Hiroaki Hatano, Yusuke Takeshima, Mai Okubo, Satomi Kobayashi, Yusuke Sugimori, Nakano Masahiro, Ryochi Yoshida, Norio Hanata, Yuichi Suwa, Yumi Tsuchida, Yukiko Iwasaki, Shuji Sumitomo, Kanae Kubo, Kenichi Shimane, Keigo Setoguchi, Takanori Azuma, Hiroko Kanda, Hirofumi Shoda, Xuan Zhang, Kazuhiko Yamamoto, Kazuyoshi Ishigaki, Tomohisa Okamura, Keishi Fujio
Summary: By analyzing the transcriptome of peripheral blood immune cell subsets in patients with rheumatoid arthritis (RA), immune cells that predict treatment resistance were identified. Changes in the transcriptome and treatment effects in RA were characterized. Plasmacytoid dendritic cells (pDC) showed the strongest association with treatment resistance. The predictive value of pDC-related gene expression and pDC proportion in treatment-resistant patients was validated in independent cohorts.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Editorial Material
Medicine, General & Internal
Shinji Izuka, Bunki Natsumoto, Hirofumi Shoda, Keishi Fujio
Letter
Rheumatology
Aya Nishiwaki, Toshihiko Komai, Yasuo Nagafuchi, Yumi Tsuchida, Hirofumi Shoda, Keishi Fujio
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES
(2023)
Letter
Rheumatology
I Takazawa, T. Komai, M. Misaki, M. Kono, H. Shoda, K. Fujio
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Letter
Allergy
Sayaka Tsuzuki, Toshihiko Komai, Aya Nishiwaki, Terumi Kamisawa, Hirofumi Shoda, Keishi Fujio, Keigo Setoguchi
ALLERGOLOGY INTERNATIONAL
(2023)
Review
Medicine, General & Internal
Kazuyuki Nakagome, Keishi Fujio, Makoto Nagata
Summary: Allergen immunotherapy (AIT) is a treatment for allergic diseases that involves administering clinical allergens to patients. It can modify allergen-specific immune responses and alleviate symptoms of allergic diseases such as asthma and rhinitis. AIT has also been shown to suppress sensitization to new allergens, indicating its potential in nonspecific suppression of allergic immune responses.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Keishi Fujio
Summary: Systemic lupus erythematosus (SLE) is a complex autoimmune disease influenced by both genetic and environmental factors. Recent analysis has revealed the significance of the oxidative phosphorylation (OXPHOS) pathway in the pathogenesis of SLE, showing persistent activation in inactive SLE and its association with organ damage. The discovery that hydroxychloroquine (HCQ), which improves SLE prognosis, targets toll-like receptor (TLR) signaling upstream of OXPHOS highlights the clinical importance of this pathway. Further studies on OXPHOS-associated disease-susceptibility polymorphisms, gene expression, and protein function may aid in risk stratification of SLE.
Review
Medicine, General & Internal
Yumi Tsuchida, Hirofumi Shoda, Tetsuji Sawada, Keishi Fujio
Summary: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by the production of autoantibodies and immune complex deposition. Autotaxin (ATX), which catalyzes the production of lysophosphatidic acid, has been identified as a potential biomarker in SLE. Increased levels of ATX have been found in the serum and urine of patients with SLE and lupus nephritis. Recent studies suggest that ATX produced by plasmacytoid dendritic cells may have an important role in SLE pathogenesis, and it is associated with type I interferons. ATX may be a valuable biomarker and key molecule in SLE.
FRONTIERS IN MEDICINE
(2023)
Article
Rheumatology
Mineto Ota, Masahiro Nakano, Yasuo Nagafuchi, Satomi Kobayashi, Hiroaki Hatano, Ryochi Yoshida, Yuko Akutsu, Takahiro Itamiya, Nobuhiro Ban, Yumi Tsuchida, Hirofumi Shoda, Kazuhiko Yamamoto, Kazuyoshi Ishigaki, Tomohisa Okamura, Keishi Fujio
Summary: This study constructed a large-scale repertoire catalogue of five B cell subsets of patients with immune-mediated diseases (IMDs) and investigated their biological mechanisms. The results showed that autoimmune diseases were associated with a shortened CDR-H3 length in naive B cells and a negative correlation between interferon signature strength and CDR-H3 length, suggesting the role of interferon in premature B cell development. The study also found gene usage skewing in plasmablasts and unswitched-memory B cells of patients with systemic lupus erythematosus (SLE), and this skewing was ameliorated after belimumab treatment.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Bunki Natsumoto, Hirofumi Shoda, Yasuo Nagafuchi, Mineto Ota, Takashi Okumura, Yumi Horie, Tomohisa Okamura, Kazuhiko Yamamoto, Motonori Tsuji, Makoto Otsu, Hideki Taniguchi, Keishi Fujio
Summary: In this study, patient-derived induced pluripotent stem cells (iPSCs) were used in combination with genetic analysis to identify and elucidate the biological functions of rare variants underlying systemic lupus erythematosus (SLE). It was found that a rare variant in the OASL gene was shared between SLE-iPSCs and another independent SLE patient, and there was a significant accumulation of OASL variants among SLE patients. Additionally, genome editing experiments confirmed the impact of these variants on type 1 interferon secretion in immune cells.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Rheumatology
Yusuke Sugimori, Yukiko Iwasaki, Yusuke Takeshima, Mai Okubo, Satomi Kobayashi, Hiroaki Hatano, Saeko Yamada, Masahiro Nakano, Ryochi Yoshida, Mineto Ota, Yumi Tsuchida, Yasuo Nagafuchi, Kenichi Shimane, Ken Yoshida, Daitaro Kurosaka, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Tomohisa Okamura, Keishi Fujio
Summary: Transcriptome analysis identified common or specific immunological pathways in different immune cell types of patients with idiopathic inflammatory myopathies (IIM) based on their clinical phenotypes and myositis-specific antibodies (MSAs). B cells may play a significant role in both common and specific immunological pathways in IIM.
ACR OPEN RHEUMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Mariko Inoue, Yasuo Nagafuchi, Mineto Ota, Haruka Tsuchiya, Shoko Tateishi, Hiroko Kanda, Keishi Fujio
Summary: HLA-DRB1 * 04:05 allele is significantly associated with better disease improvement in abatacept-treated patients with rheumatoid arthritis. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy.
SCIENTIFIC REPORTS
(2023)
