Article
Medicine, General & Internal
Xinghui Song, Hui Zhang, Yun Zhao, Yuanzhen Lin, Qiya Tang, Xiu Zhou, Xiaoning Zhong
Summary: The study found that HMGB1 can activate myeloid dendritic cells by upregulating the mTOR pathway in peripheral blood of SLE patients, leading to increased production of pro-inflammatory cytokines. Rapamycin was able to inhibit HMGB1-induced activation of dendritic cells and secretion of pro-inflammatory cytokines.
FRONTIERS IN MEDICINE
(2021)
Review
Immunology
Swayanka Biswas, Katja Bieber, Rudolf Armin Manz
Summary: IL-10 is a cytokine that has pleiotropic effects on immune cells, including both suppressive and activating functions. It plays a dual role in Systemic lupus Erythematosus (SLE), inhibiting pro-inflammatory effector functions while also promoting extrafollicular antibody response. IL-10 is produced by B cells, myeloid cells, and certain T cell subsets, and it drives B cell responses, proliferation, class switching, and plasma cell formation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Wenqian Wang, Chenran Yue, Sheng Gao, Shuting Li, Jianan Zhou, Jiaqing Chen, Jiahong Fu, Weijian Sun, Chunyan Hua
Summary: Exosomal miRNAs show potential as biomarkers in SLE/LN patients for renal injury diagnosis. Exosomes are considered optimal delivery vehicles due to their high stability, minimal toxicity, low immunogenicity, and specific target effects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Satish Pasula, Jaanam Gopalakrishnan, Yao Fu, Kandice L. Tessneer, Mandi M. Wiley, Richard C. Pelikan, Jennifer A. Kelly, Patrick M. Gaffney
Summary: This study demonstrates the complex chromatin regulatory network at the TNFAIP3 locus and its role in autoimmune disease pathology. SNPs on this locus can lead to upregulation of certain genes while suppressing TNFAIP3 expression, highlighting the mechanistic potency of this locus in autoimmune diseases.
FRONTIERS IN GENETICS
(2022)
Article
Immunology
Meiyu Wu, Wenjing Pan, Chen Jia, Zhenghao He, Ming Zhao, Congli Tang, Christopher Chang, Song Li, Haijing Wu, Qianjin Lu
Summary: Our study demonstrates that changes in immune repertoire during treatment can serve as surrogate biomarkers for disease response in systemic lupus erythematosus (SLE) patients. The sensitive and nonsensitive groups showed different responses in B cell receptor (BCR) expression, IgM and IgA composition, CDR3 length, and immune-related gene expression levels after immunosuppressive drug treatment.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Rheumatology
Lingxiao Xu, Jian Zhao, Qing Sun, Xue Xu, Lei Wang, Ting Liu, Yunjuan Wu, Jingfeng Zhu, Linyu Geng, Yun Deng, Alexander Awgulewitsch, Diane L. Kamen, Jim C. Oates, Prithvi Raj, Edward K. Wakeland, R. Hal Scofield, Joel M. Guthridge, Judith A. James, Bevra H. Hahn, Deborah K. McCurdy, Fang Wang, Miaojia Zhang, Wenfeng Tan, Gary S. Gilkeson, Betty P. Tsao
Summary: This research found two novel SAT1 LOF variants through whole exome sequencing in families with multiple siblings affected by systemic lupus erythematosus (SLE), demonstrating their association with SLE. The study highlights the pathogenic role of dysregulated polyamine catabolism in lupus.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Quentin Moyon, Delphine Sterlin, Makoto Miyara, Francois Anna, Alexis Mathian, Raphael Lhote, Pascale Ghillani-Dalbin, Paul Breillat, Sasi Mudumba, Sophia de Alba, Fleur Cohen-aubart, Julien Haroche, Micheline Pha, Thi Huong Du Boutin, Hedi Chaieb, Pedro Macedo Flores, Pierre Charneau, Guy Gorochov, Zahir Amoura
Summary: This study evaluated disease activity and immune responses in SLE patients following BNT162b2 vaccination. MMF and MTX treatments were found to be associated with reduced antibody response, while anti-spike antibody response was positively correlated with baseline immunoglobulin levels, naive B cell frequencies, and SARS-CoV-2-specific T cell response.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Review
Rheumatology
Fan Yang, Jin Lin, Weiqian Chen
Summary: Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized by multiple autoantibodies and immune-mediated tissue damage. While a new drug, belimumab, shows promise in improving SLE conditions, the discovery of novel therapeutic targets is urgently needed. Protein post-translational modifications (PTMs) may play key roles in regulating T-cell function and signaling pathways in SLE pathogenesis, presenting potential new targets for therapy.
Review
Immunology
Paul Curtiss, Amanda M. Walker, Benjamin F. Chong
Summary: This study reviewed patient cohorts and populations to investigate the progression of cutaneous lupus to systemic lupus. The study found variations in the progression rates between adult and pediatric groups, which were attributed to differences in patient populations, study design, diagnostic criteria, and follow-up time. Risk factors associated with the development of systemic lupus included positive anti-nuclear antibodies, hematologic abnormalities, and a higher number of lupus classification criteria at baseline.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Ying Teng, Zi-Ye Yan, Lin-Lin Wang, Yu-Hua Wang, Ting-Yu Zhang, Zhen Li, Shuang Liu, Jing Cai, Yang-Fan Chen, Mu Li, Sheng-Xiu Liu, Zhou-Zhou Xu, Hai-Liang Huang, Fang Wang, Fa-Ming Pan, Hai-Feng Pan, Hong Su, Yan-Feng Zou
Summary: This study investigated the associations of mitochondrial DNA (mtDNA) genetic variants with SLE susceptibility, glucocorticoid efficacy, and prognosis. The researchers identified several mtDNA variants that were associated with SLE susceptibility, glucocorticoid efficacy, and relapse risk. They also observed interactions between mtDNA variants and environmental factors. These findings provide important information for understanding the occurrence and development of SLE.
Article
Rheumatology
Huai-Chia Chuang, Wei-Ting Hung, Yi-Ming Chen, Pu-Ming Hsu, Jeng-Hsien Yen, Joung-Liang Lan, Tse-Hua Tan
Summary: Multiple germline and somatic variants of the MAP4K3 (GLK) gene were found in patients with SLE, leading to increased GLK expression through mRNA or protein stability.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Immunology
Hao Li, Afroditi Boulougoura, Yushiro Endo, George C. Tsokos
Summary: T cell abnormalities are closely associated with the development of SLE, including numerical and functional disturbances in CD4+ and CD8+ T cells, which lead to immune dysregulation and tissue infiltration. These abnormalities are mainly due to signaling defects, metabolic alterations, and epigenetic changes. Novel strategies to correct T cell abnormalities show promise for SLE treatment.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Rheumatology
Ming Zhao, Delong Feng, Longyuan Hu, Lin Liu, Jiali Wu, Zhi Hu, Haojun Long, Qiqi Kuang, Lianlian Ouyang, Qianjin Lu
Summary: This study aimed to elucidate the three-dimensional genome structure and its impact on gene expression networks in systemic lupus erythematosus (SLE). Through analysis of CD4(+) T cells from SLE patients and healthy controls, it was found that SLE patients had distinct genome structures compared to healthy controls, which were closely associated with disease activity. Additionally, loops within chromosomes associated with disease activity and differentially expressed genes were identified, along with key histone modifications close to these loops. The study provides a foundation for further investigation into the relationship between chromosome structure and gene expression control in SLE.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Oncology
Kaichi Kaneko, Hao Chen, Matthew Kaufman, Isaak Sverdlov, Emily M. Stein, Kyung-Hyun Park-Min
Summary: Osteonecrosis is a complex and devastating complication of systemic lupus erythematosus, with variable prevalence in SLE patients. The use of high-dose glucocorticoid therapy is strongly associated with the development of osteonecrosis in SLE patients, although the exact pathophysiology and risk factors for osteonecrosis in this population are not fully understood.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Valeria Rella, Cinzia Rotondo, Alberto Altomare, Francesco Paolo Cantatore, Addolorata Corrado
Summary: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations. Dysregulation of the immune system due to genetic, hormonal, and environmental factors can lead to various complications, including bone involvement such as osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Rheumatology
Peter C. Taylor, Tsutomu Takeuchi, Gerd R. Burmester, Patrick Durez, Josef S. Smolen, Walter Deberdt, Maher Issa, Jorge Ross Terres, Natalia Bello, Kevin L. Winthrop
Summary: This study reported long-term safety data of baricitinib in patients with active RA, including analysis of various adverse events and assessment of malignancy risk. The conclusions indicated that baricitinib maintained a stable safety profile similar to earlier analyses, with no new safety signals identified.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Daniel Aletaha, Andreas Kerschbaumer, Kastriot Kastrati, Christian Dejaco, Maxime Dougados, Iain B. McInnes, Naveed Sattar, Tanja A. Stamm, Tsutomu Takeuchi, Michael Trauner, Desiree van der Heijde, Marieke Voshaar, Kevin L. Winthrop, Angelo Ravelli, Neil Betteridge, Gerd-Ruediger R. Burmester, Johannes W. J. Bijlsma, Vivian Bykerk, Roberto Caporali, Ernest H. Choy, Catalin Codreanu, Bernard Combe, Mary K. Crow, Maarten de Wit, Paul Emery, Roy M. Fleischmann, Cem Gabay, Merete Lund Hetland, Kimme L. Hyrich, Annamaria Iagnocco, John D. Isaacs, Joel M. Kremer, Xavier Mariette, Peter Merkel, Eduardo F. Mysler, Peter Nash, Michael T. Nurmohamed, Karel Pavelka, Gyula Poor, Andrea Rubbert-Roth, Hendrik Schulze-Koops, Anja Strangfeld, Yoshiya Tanaka, Josef S. Smolen
Summary: This paper is an updated consensus document on the medical use of IL-6 pathway inhibition in the treatment of inflammatory diseases. The document provides comprehensive consensus statements based on systematic literature research and expert opinion, covering various aspects of IL-6 pathway inhibitors, including dosing, indications, and clinical considerations.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Yoshiya Tanaka, Masafumi Kawanishi, Megumi Nakanishi, Hironori Yamasaki, Tsutomu Takeuchi
Summary: Subcutaneous ozoralizumab treatment for 52 weeks demonstrated significant therapeutic effects and acceptable tolerability in patients with active rheumatoid arthritis.
MODERN RHEUMATOLOGY
(2023)
Review
Rheumatology
Sytske Anne Bergstra, Alexandre Sepriano, Andreas Kerschbaumer, Desiree van der Heijde, Roberto Caporali, Christopher John Edwards, Patrick Verschueren, Savia de Souza, Janet E. Pope, Tsutomu Takeuchi, Kimme L. Hyrich, Kevin L. Winthrop, Daniel Aletaha, Tanja A. Stamm, Jan W. Schoones, Josef S. Smolen, Robert B. M. Landewe
Summary: This systematic literature review examines the efficacy, duration of use, and safety of glucocorticoids (GCs) in the management of rheumatoid arthritis (RA). The study confirms the effectiveness of GCs in treating RA, with most patients able to stop GCs within 12-24 months. However, the use of GCs also carries well-known safety risks, including osteoporotic fractures, serious infections, diabetes, and mortality.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Tsutomu Takeuchi, Sakae Tanaka, Mitsuru Murata, Yoshiya Tanaka
Summary: This study aimed to evaluate the efficacy and safety of TAS5315 in Japanese patients with refractory rheumatoid arthritis. The results showed numerical differences in disease activity improvement rates between the TAS5315 group and the placebo group at week 12, but the primary endpoint was not achieved. However, TAS5315 demonstrated advantages in disease activity and biomarker improvement, as well as higher risk of bleeding events within 36 weeks. Therefore, a risk-benefit analysis of TAS5315 should be considered.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Yoshiya Tanaka, Tsutomu Takeuchi, Derek Haaland, Stephen Hall, Nevsun Inanc, Zhanguo Li, Ricardo M. M. Xavier, Carlos Cara, Nicola Tilt, Peter C. C. Taylor
Summary: This study assessed the efficacy of Certolizumab pegol (CZP) in patients with early and established rheumatoid arthritis (RA) and found that it was effective in reducing symptoms in patients with different rheumatoid factors (RF) levels. CZP may be considered as a treatment option for RA.
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Peter C. Taylor, Michael E. Weinblatt, Iain B. McInnes, Tatsuya Atsumi, Vibeke Strand, Tsutomu Takeuchi, Marguerite Bracher, David Brooks, John Davies, Christopher Goode, Anubha Gupta, Sumanta Mukherjee, Ciara O'Shea, Didier Saurigny, Lorrie A. Schifano, Celia Shelton, Julia E. Smith, Millie Wang, Reena Wang, Sarah Watts, Roy M. Fleischmann
Summary: This study investigated the efficacy and safety of otilimab in patients with active rheumatoid arthritis. The results showed that otilimab did not achieve the primary endpoint of ACR20 and did not demonstrate non-inferiority to sarilumab in this patient population.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Satoshi Takanashi, Yasushi Kondo, Shuntaro Saito, Jun Kikuchi, Hironari Hanaoka, Tsutomu Takeuchi, Yuko Kaneko
Summary: Rituximab is an effective treatment option for patients with lymphoproliferative disorder and rheumatoid vasculitis, showing significant improvements in disease activity scores and reduction in prednisolone dosage, with a good safety profile.
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES
(2023)
Article
Pharmacology & Pharmacy
Tsutomu Takeuchi, Yukihiro Chino, Yoko Mano, Masafumi Kawanishi, Yuri Sato, Saeko Uchida, Yoshiya Tanaka
Summary: A population pharmacokinetic (PK) model was developed to assess the effects of potential PK covariates on the PK of ozoralizumab. The model adequately described the PK of ozoralizumab in Japanese patients with rheumatoid arthritis, and body weight was found to have the greatest impact on its PK.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Rheumatology
Tsutomu Takeuchi, Megumi Nakanishi, Masafumi Kawanishi, Hironori Yamasaki, Yoshiya Tanaka
Summary: This article evaluates the efficacy and safety of extending the dosing interval of ozoralizumab from every 4 weeks to every 8 weeks in patients with rheumatoid arthritis (RA). The results indicate that extending the dosing interval is effective and well tolerated in patients maintaining a disease activity score below 3.2.
MODERN RHEUMATOLOGY
(2023)
Editorial Material
Rheumatology
Marc Feldmann, Ravinder N. Maini, Enrique R. Soriano, Vibeke Strand, Tsutomu Takeuchi
Summary: In this Viewpoint article, five rheumatology researchers discuss how biologic therapy has transformed clinical practice and reflect on their own experiences, past and current challenges, and the future prospects of biologic drugs.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Rheumatology
Tsutomu Takeuchi, Yukihiro Chino, Masafumi Kawanishi, Megumi Nakanishi, Hirotaka Watase, Yoko Mano, Yuri Sato, Saeko Uchida, Yoshiya Tanaka
Summary: This study aimed to analyze the pharmacokinetics (PK) of Ozoralizumab (OZR) and its correlation with clinical efficacy in rheumatoid arthritis (RA) patients. The results showed that the maximum plasma concentration (C-max) of OZR was reached in 6 days, with a half-life of 18 days. The exposure of OZR correlated negatively with patient body weight and was not significantly affected by other patient baseline characteristics. The efficacy of OZR was sustained independent of trough concentration when administered subcutaneously at a dose of 30 mg every 4 weeks for 52 weeks.
ARTHRITIS RESEARCH & THERAPY
(2023)
Review
Immunology
Tsutomu Takeuchi
Summary: This review provides an overview of cytokines and cytokine receptors approved in immune-mediated inflammatory diseases (IMID) and discusses their role, treatment modalities, and updated molecular information in each disease, with rheumatoid arthritis as a role model.
INFLAMMATION AND REGENERATION
(2022)
Article
Rheumatology
Tsutomu Takeuchi, Masafumi Kawanishi, Megumi Nakanishi, Hironori Yamasaki, Yoshiya Tanaka
Summary: This study assessed the efficacy and safety of ozoralizumab plus methotrexate in patients with active rheumatoid arthritis. The results showed that ozoralizumab significantly reduced the signs and symptoms of RA compared to placebo, with acceptable tolerability.
ARTHRITIS & RHEUMATOLOGY
(2022)
Article
Rheumatology
Yoshiya Tanaka, Tsutomu Takeuchi, Daisuke Kato, Yuichiro Kaneko, Musashi Fukuda, Daisuke Miyatake
Summary: The study evaluated the efficacy and safety of peficitinib treatment in Asian patients with rheumatoid arthritis, showing that peficitinib demonstrated efficacy improvements compared to placebo regardless of age. However, the incidence rates of serious infections and herpes zoster-related disease significantly increased with age.
MODERN RHEUMATOLOGY
(2022)
