Article
Rheumatology
Maya Malaab, Ludivine Renaud, Naoko Takamura, Kip D. Zimmerman, Willian A. da Silveira, Paula S. Ramos, Sandra Haddad, Marc Peters-Golden, Loka R. Penke, Bethany Wolf, Gary Hardiman, Carl D. Langefeld, Thomas A. Medsger, Carol A. Feghali-Bostwick
Summary: Our study identified distinct molecular features in dermal fibroblasts of systemic sclerosis patients, including dysregulated transcription factors and microRNAs, suggesting a role for epigenetic dysregulation in disease susceptibility. This highlights the potential for using epigenetic modifiers as future therapies in systemic sclerosis.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Dermatology
Xuefen Wu, Bingxia Ming, Tong Wu, Rongfen Gao, Peng Hu, Jungen Tang, Jixin Zhong, Fang Zheng, Lingli Dong
Summary: IL-33/ST2 axis plays a crucial role in the fibrotic disorder of SSc by promoting fibroblast activation, and IL-33/ST2 blockade could be a potential novel strategy to inhibit fibrosis progression in SSc patients.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Genevieve A. Secker, Natasha L. Harvey
Summary: The importance of lymphatic vessels in human diseases, the initiation of lymphatic vascular development during embryogenesis, and the role of VEGF/VEGFR signaling in driving the construction of lymphatic vessels were discussed in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Mehmet Can Ucar, Edouard Hannezo, Emmi Tiilikainen, Inam Liaqat, Emma Jakobsson, Harri Nurmi, Kari Vaahtomeri
Summary: The authors reveal that developing lymphatic capillary networks utilize complementary branching strategies to optimize tissue coverage through a combination of experimental and theoretical approaches.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Margarita Barriga, Raquel Benitez, Gema Robledo, Marta Caro, Francisco O'Valle, Jenny Campos-Salinas, Mario Delgado
Summary: This study investigates the role of the neuropeptide cortistatin in scleroderma. The findings suggest that cortistatin acts as an endogenous regulator of skin inflammation and fibrosis. Deficiency in cortistatin may indicate a poor prognosis for scleroderma and its associated complications. Cortistatin-based therapies may be potential treatments for severe systemic sclerosis and for managing fibrosis-related side effects in oncology patients receiving bleomycin chemotherapy.
NEUROENDOCRINOLOGY
(2022)
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.
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)
Article
Rheumatology
Barbara Russo, Julia Borowczyk, Pietro Cacialli, Philippe Moguelet, Marie-Elise Truchetet, Ali Modarressi, Nicolo C. Brembilla, Julien Bertrand, Wolf-Henning Boehncke, Carlo Chizzolini
Summary: IL-25 plays a role in regulating skin fibrosis, and its decreased expression in systemic sclerosis may contribute to the excessive accumulation of extracellular matrix and progress of fibrosis.
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
Immunology
Naoko Takamura, Ludivine Renaud, Willian Abraham da Silveira, Carol Feghali-Bostwick
Summary: Systemic sclerosis is an autoimmune disease characterized by vasculopathy and excessive fibrosis, with limited treatment options available. Research suggests that abnormal regulation of MCHR1 may play a role in the pathogenesis of SSc, and inhibiting MCHR1 could be a novel therapeutic strategy.
FRONTIERS IN IMMUNOLOGY
(2021)
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.
Review
Health Care Sciences & Services
Francesco Reggiani, Gabriella Moroni, Claudio Ponticelli
Summary: Systemic sclerosis is a chronic autoimmune disease that often involves the kidneys. Scleroderma renal crisis is the most serious renal event associated with this condition, and early and aggressive treatment is necessary to prevent irreversible organ damage and death.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
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)
Article
Immunology
Fatemeh Vafashoar, Kazem Mousavizadeh, Hadi Poormoghim, Amir Haghighi, Salar Pashangzadeh, Nazanin Mojtabavi
Summary: The study found that progesterone treatment increased collagen content in fibrotic and normal lung tissues, as well as increased alpha-SMA and TGF-beta in fibrotic lung tissues while decreasing MMP9. Furthermore, progesterone treatment also decreased the gene expression of Col1a2, Ctgf, and End1 in bleomycin-injured lung tissues.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Serena Fineschi
Summary: COVID-19 infection can trigger autoimmune diseases like systemic sclerosis (SSc) and lead to the production of autoantibodies. This case report describes a patient who developed autoantibody production and symptoms affecting the skin and gastrointestinal system after mild COVID-19 infection, eventually being diagnosed with SSc.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Eloisa Romano, Irene Rosa, Bianca Saveria Fioretto, Dilia Giuggioli, Mirko Manetti, Marco Matucci-Cerinic
Summary: Pharmacological sGC stimulation effectively improves the angiogenic performance and reduces the myofibroblast-like profibrotic phenotype of SSc-MVECs, providing new evidence for repurposing sGC stimulators for the treatment of SSc.
Review
Biochemistry & Molecular Biology
Bianca Saveria Fioretto, Irene Rosa, Marco Matucci-Cerinic, Eloisa Romano, Mirko Manetti
Summary: Systemic sclerosis (SSc, scleroderma) is a rare connective tissue disease characterized by immune dysregulation, small vessel vasculopathy, impaired angiogenesis, and fibrosis. Microvascular impairment is the initial event of the disease and is linked to disabling and life-threatening clinical manifestations. Despite available treatment options, managing SSc-related vascular disease remains challenging. Vascular biomarkers have shown promise in assessing disease progression, predicting prognosis, and guiding therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Rheumatology
Edda Russo, Silvia Bellando-Randone, Davide Carboni, Bianca Saveria Fioretto, Eloisa Romano, Simone Baldi, Khadija El Aoufy, Matteo Ramazzotti, Irene Rosa, Gemma Lepri, Leandro Di Gloria, Marco Pallecchi, Cosimo Bruni, Daniela Melchiorre, Serena Guiducci, Mirko Manetti, Gian Luca Bartolucci, Marco Matucci-Cerinic, Amedeo Amedei
Summary: This study characterized the microbiota in SSc patients and found different microbiota profiles and FFA profiles between ACA+ and anti-Scl70+ groups. The cutaneous Sphingobacteria and faecal Lentisphaerae were interdependent in ACA+ patients. The findings suggest a potential role of the microbiota and FFAs in the pathogenesis of SSc.
Article
Cell Biology
Elena Andreucci, Bianca Saveria Fioretto, Irene Rosa, Marco Matucci-Cerinic, Alessio Biagioni, Eloisa Romano, Lido Calorini, Mirko Manetti
Summary: This study reveals a previously unrecognized relationship between lactic acidosis and the generation of a new CAF-like cell subpopulation from adipocytic precursor cells, which sustains tumor malignancy.
Editorial Material
Biology
Eloisa Romano, Irene Rosa, Mirko Manetti
Article
Cell Biology
Irene Rosa, Patrizia Nardini, Bianca Saveria Fioretto, Daniele Guasti, Eloisa Romano, Eleonora Sgambati, Mirca Marini, Mirko Manetti
Summary: Telocytes (TCs) have been found to exist in the stromal tissue of the human vaginal mucosa and are characterized by their presence in the perivascular networks and release of extracellular vesicles. Further investigation is needed to determine the functions of TCs in vaginal mucosal homeostasis and pathophysiology.
Article
Cell Biology
Irene Rosa, Eloisa Romano, Bianca Saveria Fioretto, Khadija El Aoufy, Silvia Bellando-Randone, Marco Matucci-Cerinic, Mirko Manetti
Summary: Currently, only a few studies have investigated the role of the lymphatic vascular system in the pathogenesis of systemic sclerosis (SSc). This study aimed to explore the possibility of lymphatic endothelial cells undergoing an endothelial-to-myofibroblast transition (Ly-EndMT) and contributing to skin fibrosis in SSc. The results demonstrated the presence of lymphatic endothelial cells in intermediate stages of the Ly-EndMT process exclusively in the fibrotic skin of SSc patients, suggesting that Ly-EndMT might be a previously overlooked pathogenic process linking peripheral microlymphatic dysfunction and skin fibrosis development in SSc.
Letter
Rheumatology
Mirko Manetti
ANNALS OF THE RHEUMATIC DISEASES
(2023)