Article
Rheumatology
Burcu Ayoglu, Michele Donato, Daniel E. Furst, Leslie J. Crofford, Ellen Goldmuntz, Lynette Keyes-Elstein, Judith James, Susan Macwana, Maureen D. Mayes, Peter McSweeney, Richard A. Nash, Keith M. Sullivan, Beverly Welch, Ashley Pinckney, Rong Mao, Lorinda Chung, Purvesh Khatri, Paul J. Utz
Summary: Results from the SCOT clinical trial showed that HSCT had significant benefits over CTX in patients with systemic sclerosis. The objective of this study was to test the hypothesis that transplantation stabilizes the autoantibody repertoire in patients with favorable clinical outcomes. Analysis of autoantibody profiles revealed significant differences between HSCT and CTX-treated patients, suggesting that HSCT alters the autoantibody repertoire while CTX treatment does not.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Immunology
Claire F. Beesley, Nina R. Goldman, Taher E. Taher, Christopher P. Denton, David J. Abraham, Rizgar A. Mageed, Voon H. Ong
Summary: Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by excessive extracellular matrix deposition. B cells play a fundamental role in the pathogenesis and development of SSc, as they infiltrate lesional sites and produce profibrotic cytokines. B cell counts are increased in SSc patients and show differences in various B cell compartments. B cell signaling is impaired in SSc patients, and B cell depletion therapy has shown therapeutic benefits.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Pawel Zebryk, Piotr Przymuszala, Jan Krzysztof Nowak, Tomasz Piorunek, Tatiana Mularek-Kubzdela, Mariusz Puszczewicz
Summary: This study evaluated the prevalence and clinical significance of SSc-related autoantibodies and compared the sensitivity of two line immunoblot assays. The findings indicate that different autoantibodies are associated with specific characteristics of SSc.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Michele Simon, Christian Luecht, Isa Hosp, Hongfan Zhao, Dashan Wu, Harald Heidecke, Janusz Witowski, Klemens Budde, Gabriela Riemekasten, Rusan Catar
Summary: Autoantibodies against PAR-1 found in patients with SSc and SRC induce IL-6 production by endothelial cells through signaling pathways controlled by the AP-1 transcription factor. These observations offer a greater understanding of adverse endothelial cell responses to autoantibodies present in patients with SRC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Rheumatology
Brittany L. Adler, Francesco Boin, Paul J. Wolters, Clifton O. Bingham, Ami A. Shah, Carol Greider, Livia Casciola-Rosen, Antony Rosen
Summary: Autoantibodies targeting telomere-associated proteins are found in a subset of patients with systemic sclerosis (SSc), and are associated with short lymphocyte telomere length and lung disease. These autoantibodies are rarely present in rheumatoid arthritis, myositis, and healthy controls, suggesting a specificity for SSc and idiopathic pulmonary fibrosis (IPF).
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Rheumatology
Kristina Elizabeth Neergaard Clark, Shiwen Xu, Moustafa Attah, Voon H. Ong, Christopher Dominic Buckley, Christopher P. Denton
Summary: This study investigated cellular differences in diffuse cutaneous systemic sclerosis (dcSSc) patients compared with healthy controls (HCs), and found differences in cell clusters between the ARA+ and ATA+ subsets, highlighting the importance of considering antibodies and disease stage in the management and trial design of dcSSc.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Medicine, General & Internal
Kholoud Almaabdi, Zareen Ahmad, Sindhu R. Johnson
Summary: Systemic sclerosis is an autoimmune disease characterized by immune abnormalities, vasculopathy, and fibrosis. Autoantibody testing, including ANA, anti-Scl-70, and anticentromere antibodies, has become increasingly important for diagnosis and prognostication. This review examines the epidemiology, clinical associations, and prognostic value of advanced autoantibody testing in systemic sclerosis.
Review
Rheumatology
George Iliopoulos, Dimitrios Daoussis
Summary: Research has shown limited data about renal impairment in SSc beyond scleroderma renal crisis (SRC). However, studies indicate that renal dysfunction in SSc is not uncommon, with a significant percentage of patients having decreased glomerular filtration rate (GFR). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula is suggested as a suitable tool for assessing renal function in SSc patients.
RHEUMATOLOGY INTERNATIONAL
(2021)
Article
Rheumatology
Sophie I. E. Liem, Sam Neppelenbroek, Cynthia M. Fehres, Brigitte A. Wevers, Rene E. M. Toes, Cornelia F. Allaart, Tom W. J. Huizinga, Hans Ulrich Scherer, Jeska K. De Vries-Bouwstra
Summary: Early diagnosis of systemic sclerosis (SSc) is important. The most frequent SSc-specific autoantibodies are anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA). ATA is associated with severe disease course. More detailed characterisation of the ATA-response in SSc might improve prognostication.
Article
Medicine, Research & Experimental
Masataka Kuwana, Aiko Saito, Wataru Sakamoto, Christina Raabe, Kumiko Saito
Summary: This study estimated the incidence and prevalence rates of systemic sclerosis (SSc) and SSc-associated interstitial lung disease (SSc-ILD) in Japan using medical databases. The results showed that approximately 30% of SSc patients had ILD, and the utilization of immunomodulatory medications was low.
ADVANCES IN THERAPY
(2022)
Article
Allergy
Alice Cole, Voon H. Ong, Christopher P. Denton
Summary: Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a high mortality rate. Although angiotensin-converting enzyme inhibitor therapy has improved renal outcomes, there are currently no preventative measures and patients may rapidly decline. Studies have identified specific phenotypes at higher risk of developing SRC and novel urinary biomarkers may aid in early identification and treatment. Clear guidelines for management have been established to standardize care and promote collaboration between rheumatology and renal physicians. While outcomes following renal transplant have improved, further research is needed to understand the mechanisms and develop new therapies for SRC.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2023)
Article
Rheumatology
Christopher P. Denton, Shiwen Xu, Fenge Zhang, Rory H. Maclean, Kristina E. N. Clark, Signe Borchert, Rizwan Hussain, Joerg Klingelhofer, Jonas Hallen, Voon H. Ong
Summary: This study investigated the role of S100A4 in fibroblast activation in systemic sclerosis (SSc). The results showed that S100A4 concentration was higher in SSc patients compared to healthy controls, and was associated with interstitial lung disease and scleroderma renal crisis. In vitro experiments demonstrated that S100A4 promoted the expression of profibrotic genes in SSc fibroblasts, while a neutralizing antibody against S100A4 reduced this expression. These findings provide evidence for the profibrotic role of S100A4 in SSc and suggest its potential as a therapeutic target.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Patrick Coit, Kaila L. Schollaert, Emily M. Mirizio, Kathryn S. Torok, Amr H. Sawalha
Summary: The study assessed DNA methylation differences between juvenile systemic sclerosis (jSSc) and juvenile localized scleroderma (jLS), revealing distinct epigenetic patterns and unique methylated genes in both diseases. Compared to healthy controls, differential methylation sites and genes were identified in jSSc and jLS, indicating potential novel diagnostic biomarkers for localized scleroderma. Pathway analysis showed enrichment of inflammatory pathways in jSSc and the HIPPO signaling pathway in jLS, highlighting different biological processes involved in each condition.
CLINICAL IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Mahmoud Nassar, Victoria Ghernautan, Nso Nso, Akwe Nyabera, Francisco Cuevas Castillo, Wan Tu, Luis Medina, Camelia Ciobanu, Mostafa Alfishawy, Vincent Rizzo, Saphwat Eskaros, Mamdouh Mahdi, Mohamed Khalifa, Mohamed El-Kassas
Summary: The gastrointestinal tract is frequently affected in individuals with systemic/localized scleroderma, leading to various GI manifestations and complications. Females are more susceptible to developing scleroderma, and esophageal and intestinal symptoms are common. Abnormal bowel movement and bacterial overgrowth contribute to malabsorption and increased mortality rate. Fecal incontinence is a common symptom that can lead to depression.
Article
Rheumatology
Robyn T. Domsic, Shiyao Gao, Maureen Laffoon, Steven Wisniewski, Yuqing Zhang, Virginia Steen, Robert Lafyatis, Thomas A. Medsger
Summary: Regardless of whether the first SSc manifestation or first non-Raynaud manifestation is used to define disease onset, a disease duration of less than 18 months at enrollment is preferable. A longer disease duration criterion more frequently results in regression to the mean of the mRSS score, which likely contributes to negative trial outcomes.
Editorial Material
Dermatology
Yuri Shimizu, Yorihisa Kotobuki, Noriko Arase, Hisashi Arase, Ichiro Katayama, Manabu Fujimoto
ANNALS OF DERMATOLOGY
(2022)
Letter
Dermatology
Emi Kaneda, Kyoko Tonomura, Yorihisa Kotobuki, Ikuko Ueda-Hayakawa, Kanako Tasaka, Manabu Fujimoto
JOURNAL OF DERMATOLOGY
(2022)
Editorial Material
Dermatology
Tatsuya Ogawa, Yosuke Ishitsuka, Yoshiyuki Nakamura, Rei Watanabe, Naoko Okiyama, Yasuhiro Fujisawa, Manabu Fujimoto, Dennis R. Roop, Toshifumi Nomura
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Dermatology
Kazunori Yokoi, Noriko Arase, Takashi Shimbo, Manabu Fujimoto, Atsushi Tanemura
ACTA DERMATO-VENEREOLOGICA
(2023)
Letter
Dermatology
Takashi Matsushita, Natsumi Fushida, Motoki Horii, Kie Mizumaki
JOURNAL OF DERMATOLOGY
(2023)
Letter
Dermatology
Yutaka Matsumura, Rei Watanabe, Hanako Koguchi-Yoshioka, Yuumi Nakamura, Aki Saito, Miki Kume, Shuichi Nakai, Yosuke Ishitsuka, Junichi Furuta, Manabu Fujimoto
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Review
Allergy
Wah Wah Aung, Yasuhito Hamaguchi, Takashi Matsushita
Summary: This review provides an overview of the immune pathogenesis of systemic sclerosis (SSc) and discusses targeted anti-cytokine therapy, with a focus on the emerging role of JAK-STAT inhibitors as potential therapeutic agents for reversing the disease.
JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY
(2023)
Article
Dermatology
Yasushi Kikuchi, Tomoki Tamakoshi, Ryuichi Ishida, Ryosuke Kobayashi, Shiho Mori, Akemi Ishida-Yamamoto, Manabu Fujimoto, Yasufumi Kaneda, Katsuto Tamai
Summary: In this study, researchers developed an ex vivo gene therapy for recessive dystrophic epidermolysis bullosa (RDEB) using autologous mesenchymal stromal cells (MSCs). The gene-modified MSCs were injected into mice with type VII collagen deficiency, leading to continuous and widespread expression of type VII collagen. The therapy showed successful application in both early blistering skin and advanced ulcerative lesions in the RDEB mouse model.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Oncology
Kazunori Yokoi, Yoshiaki Yasumizu, Naganari Ohkura, Koei Shinzawa, Daisuke Okuzaki, Nene Shimoda, Hideya Ando, Nanako Yamada, Manabu Fujimoto, Atsushi Tanemura
Summary: In this study, it was found that the skin tightness of hypopigmented lesions in vitiligo patients was more evident compared to uninvolved perilesional skin. Collagen homeostasis in vitiligo lesions appeared to be maintained despite the excessive oxidative stress associated with the disease. The expression of collagen-related genes and anti-oxidative enzymes was upregulated, collagen degeneration was attenuated, and the NRF2 signaling pathway was activated in vitiligo dermis.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Editorial Material
Rheumatology
Manabu Fujimoto
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Dermatology
Natsumi Fushida, Motoki Horii, Kyosuke Oishi, Takashi Matsushita
Summary: This study investigated the effectiveness of anifrolumab in treating systemic lupus erythematosus (SLE). The results showed that anifrolumab was effective in treating SLE, reducing SLEDAI-2 K and CLASI activity scores, and facilitating tapering of corticosteroid dosage.
JOURNAL OF DERMATOLOGY
(2023)
Article
Dermatology
Yasuhito Hamaguchi, Yukari Yoshimura, Motoki Horii, Natsumi Fushida, Tasuku Kitano, Kaori Sawada, Kyosuke Oishi, Shintaro Maeda, Satoshi Watanabe, Takashi Matsushita
Summary: Interstitial lung disease is a prognostic factor and leading cause of death in patients with systemic sclerosis. This study found that the presence of interstitial lung disease at an initial visit is an independent factor associated with disease deterioration.
JOURNAL OF DERMATOLOGY
(2023)
Article
Dermatology
Mari Wataya-Kaneda, Shinichirou Maeda, Ayumi Nakamura, Misa Hayashi, Manabu Fujimoto
Summary: A pilot study was conducted to evaluate the safety and efficacy of 0.2% sirolimus gel for venous and capillary malformations, and to compare its efficacy with systemic sirolimus treatment. The results showed that the gel was as clinically effective as systemic treatment and more effective for early active lesions, even systemic venous malformations.
JOURNAL OF DERMATOLOGY
(2023)
Review
Immunology
Yutaka Matsumura, Rei Watanabe, Manabu Fujimoto
Summary: B cells, including regulatory B cells (Bregs), regulate inflammation through an inhibitory mechanism mediated by interleukin 10 (IL-10). Bregs have been reported in various disease models and play a role in autoimmune diseases, infectious diseases, cancer, and organ-transplant rejection. In addition to IL-10, other cytokines and membrane-binding molecules are also involved in the suppressive functions of Bregs. The identification and classification of Breg fractions remains challenging due to the variations in their activity and differentiation stages in different disease models.
INTERNATIONAL IMMUNOLOGY
(2023)
Article
Rheumatology
Jucier Goncalves Junior, Naoki Mugii, Pleiades Tiharu Inaoka, Renata Miossi, Fernando Henrique Carlos De Souza, Joao Calvino Soares De Oliveira, Fujiko Someya, Yasuhito Hamaguchi, Takashi Matsushita, Percival Degrava Sampaio-Barros, Samuel Katsuyuki Shinjo
Summary: This study describes and compares the demographic, clinical, and laboratory characteristics of patients with Myo-SSc from two tertiary centers. The study found that Myo-SSc mainly affects middle-aged women and the manifestation spectrum varies according to geographic distribution.
ARCHIVES OF RHEUMATOLOGY
(2023)