Article
Rheumatology
Kristina Elizabeth Neergaard Clark, Corrado Campochiaro, Eszter Csomor, Adam Taylor, Katherine Nevin, Nicholas Galwey, Mary A. Morse, Jennifer Singh, Yee Voan Teo, Voon H. Ong, Emma Derrett-Smith, Nicolas Wisniacki, Shaun M. Flint, Christopher P. Denton
Summary: Clinical heterogeneity is a key feature of systemic sclerosis (SSc), with hallmark SSc autoantibodies playing a central role in diagnosis and associating with distinct patterns of complications. This study used high-dimensional transcriptional and proteomic analysis to reveal a molecular spectrum of SSc based on skin gene expression and serum protein analysis, showing differences in fibrosis markers and gene expression profiles between different autoantibody specificities. Individual patient pathway analysis identified overlapping and distinct disease processes within SSc subgroups.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Immunology
Elvira Favoino, Paola Cipriani, Vasiliki Liakouli, Addolorata Corrado, Luca Navarini, Marta Vomero, Adriana Sisto, Rosa Daniela Grembiale, Francesco Ciccia, Francesco P. Cantatore, Piero Ruscitti, Roberto Giacomelli, Federico Perosa
Summary: This study characterized the fine specificity of anti-fibroblast antibodies (AFA) and found that anti-p121 antibodies were associated with clinical parameters of systemic sclerosis (SSc), including diffuse cutaneous SSc (dcSSc), reduced FVC, and interstitial lung disease (ILD). This suggests that the antigen recognized by anti-p121 antibodies could be a potential therapeutic target for ILD.
CLINICAL IMMUNOLOGY
(2023)
Article
Rheumatology
David A. Fox, Steven K. Lundy, Michael L. Whitfield, Veronica Berrocal, Phillip Campbell, Stephanie Rasmussen, Ray Ohara, Alexander Stinson, Mikel Gurrea-Rubio, Evan Wiewiora, Catherine Spino, Erica Bush, Daniel Furst, Shiv Pillai, Dinesh Khanna
Summary: In this study, abnormalities in immune cell parameters in early diffuse cutaneous SSc patients were identified, which may reflect disease pathogenesis and serve as candidate biomarkers for sub-classification and targeted treatment. CD4+CD319+ (SLAM-F7+) cells, which are cytotoxic and oligoclonal, were found to be a dominant T cell population in perivascular lymphocytic infiltrates in SSc skin and are emerging as a target for novel treatments of SSc.
ARTHRITIS RESEARCH & THERAPY
(2021)
Article
Rheumatology
Scott A. Jenks, Chungwen Wei, Regina Bugrovsky, Aisha Hill, Xiaoqian Wang, Francesca M. Rossi, Kevin Cashman, Matthew C. Woodruff, Laura D. Aspey, S. Sam Lim, Gaobin Bao, Cristina Drenkard, Ignacio Sanz
Summary: Patients with CCLE+/SLE- exhibit similarities in B-cell abnormalities with SLE patients, although at a lower level of unswitched memory cells and increased effector B-cells. Despite lower levels of anti-nucleic acid and anti-RBP antibodies, CCLE+/SLE- patients have elevated levels of 9G4+ IgG autoantibodies.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Rheumatology
Sabrina Hoa, Selma Lazizi, Murray Baron, Mianbo Wang, Marvin J. Fritzler, Marie Hudson
Summary: There is an association between cancer and specific autoantibodies in SSc patients, with increased cancer risk in patients positive for anti-topoisomerase I and anti-U1-RNP antibodies. However, synchronous cancer is rare in this cohort of Canadian SSc patients.
Article
Biology
Sevdalina Nikolova Lambova, Ekaterina Krasimirova Kurteva, Sanie Syuleymanova Dzhambazova, Georgi Hristov Vasilev, Dobroslav Stanimirov Kyurkchiev, Mariela Gencheva Geneva-Popova
Summary: In this pilot study involving 19 patients with SSc, a correlation between more advanced capillaroscopic changes and the presence of anti-Scl-70 autoantibodies was confirmed. Additionally, positive anti-RNAP III-155 antibodies were found in SSc patients with or without early microangiopathy.
Article
Allergy
Ilaria Cavazzana, Tamara Vojinovic, Paolo Airo', Micaela Fredi, Angela Ceribelli, Eleonora Pedretti, Maria Grazia Lazzaroni, Emirena Garrafa, Franco Franceschini
Summary: Disease-specific autoantibodies are crucial biomarkers for systemic sclerosis (SSc) as they can help in diagnosing the condition and predicting its severity and prognosis. Anti-nuclear antibodies (ANA), particularly the presence of isolated Raynuad's phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage. Other specific autoantibodies like anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies are classical biomarkers for SSc and can define patients with well-described complications. The accurate detection of these autoantibodies is important for patient stratification and determining the best treatment approach.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2023)
Article
Dermatology
Karolina Pelka, Magdalena Stec-Polak, Anna Wojas-Pelc, Maciej Pastuszczak
Summary: High prevalence of AMA-M2 was found in patients with subacute cutaneous lupus erythematosus (SCLE), with significantly higher levels of cholestatic liver enzymes in AMA-M2 positive patients. Screening for AMA is recommended in newly diagnosed SCLE patients, and caution should be taken to avoid drugs with potential liver toxicity.
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2021)
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
Diana Simon, Peter Balogh, Szabina Erdo-Bonyar, Katalin Borocz, Tunde Minier, Laszlo Czirjak, Timea Berki
Summary: The study found that severe SSc patients have a higher ratio of ASM B cells, with anti-topoisomerase I antibody positive patients and those with pulmonary fibrosis having elevated ASM B cell ratios possibly associated with the severe form of the disease. The decrease in DN1 B cells ratio and the increase in anti-citrate synthase IgG autoantibody levels may have potential significance in assessing disease activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Allergy
Maria-Grazia Lazzaroni, Silvia Piantoni, Fabrizio Angeli, Stefania Bertocchi, Franco Franceschini, Paolo Airo
Summary: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by vasculopathy, immune activation, and fibrosis. The heterogeneity of the disease presents challenges in classification and defining disease outcomes. Patient-reported outcomes have been increasingly used in clinical trials to capture the patient experience. This comprehensive review covers pathogenesis, histopathology, epidemiology, classification systems, and disease outcome measures, with a focus on their relevance to clinical research and trial design.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(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
Immunology
Elopy N. Sibanda, Yvonne Dube, Mazvita Chakawa, Takafira Mduluza, Francisca Mutapi
Summary: This study investigated the clinical and laboratory characteristics of Zimbabwean patients with SSc specific autoantibodies, revealing racial variations in the expression of these antibodies. Most patients did not meet the classification criteria for SSc but still exhibited significant symptoms. Respiratory and skin symptoms were among the most common in the patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Marvin J. Fritzler, Chelsea Bentow, Lorenzo Beretta, Boaz Palterer, Janire Perurena-Prieto, Maria Teresa Sanz-Martinez, Alfredo Guillen-Del-Castillo, Ana Marin, Vicent Fonollosa-Pla, Eduardo Callejas-Moraga, Carmen Pilar Simeon-Aznar, Michael Mahler
Summary: Anti-nuclear (ANA) are important biomarkers in supporting the diagnosis and prognosis of systemic sclerosis (SSc). In addition to the well-known SSc autoantibodies, such as anti-centromere, anti-topoisomerase I (Scl-70), anti-RNA polymerase III, other autoantibodies like anti-U11/U12 ribonucleoprotein (RNP) antibodies have been associated with specific SSc phenotypes and malignancy. The U11/U12 RNP macromolecular complex is involved in alternative mRNA splicing and its antibodies have been linked to severe pulmonary fibrosis and gastrointestinal dysmotility. This literature review aims to summarize the knowledge of anti-U11/U12/RNPC-3 antibodies in SSc.
Review
Rheumatology
Alain Lescoat, Robert D. Sandler, Francois Zimmermann, David Roofeh, Michael Hughes, John D. Pauling, Susan L. Murphy, Yen T. Chen, Whitney Townsend, Maya H. Buch, Dinesh Khanna
Summary: The aim of this study was to identify instruments used to assess lcSSc, and the results show that lcSSc is underrepresented in the literature.
Review
Rheumatology
Yehya Al-Adwi, Johanna Westra, Harry van Goor, Janette K. Burgess, Christopher P. Denton, Douwe J. Mulder
Summary: SSc is a multiphase autoimmune disease characterized by vasculopathy, inflammation, and fibrosis. Macrophages play a crucial role in the pathogenesis of SSc, as they can initiate chronic inflammation and secrete fibrotic factors.
Article
Rheumatology
Caroline A. Flurey, John D. Pauling, Lesley Ann Saketkoo, Christopher P. Denton, Paul Galdas, Dinesh Khanna, Adrian Williams, Michael Hughes
Summary: This study explores the experiences, coping strategies, and support preferences of male patients with SSc. It reveals that SSc affects their masculine identity and roles, with important issues related to sex and intimacy being overlooked. Male patients are willing to accept practical help but may mask the emotional impact.
Article
Rheumatology
David Roofeh, Kevin K. Brown, Ella A. Kazerooni, Donald Tashkin, Shervin Assassi, Fernando Martinez, Athol U. Wells, Ganesh Raghu, Christopher P. Denton, Lorinda Chung, Anna-Maria Hoffmann-Vold, Oliver Distler, Kerri A. Johannson, Yannick Allanore, Eric L. Matteson, Leticia Kawano-Dourado, John D. Pauling, James R. Seibold, Elizabeth R. Volkmann, Simon L. F. Walsh, Chester Oddis, Eric S. White, Shaney L. Barratt, Elana J. Bernstein, Robyn T. Domsic, Paul F. Dellaripa, Richard Conway, Ivan Rosas, Nitin Bhatt, Vivien Hsu, Francesca Ingegnoli, Bashar Kahaleh, Puneet Garcha, Nishant Gupta, Surabhi Khanna, Peter Korsten, Celia Lin, Stephen C. Mathai, Vibeke Strand, Tracy J. Doyle, Virginia Steen, Donald F. Zoz, Juan Ovalles-Bonilla, Ignasi Rodriguez-Pinto, Padmanabha D. Shenoy, Andrew Lewandoski, Elizabeth Belloli, Alain Lescoat, Vivek Nagaraja, Wen Ye, Suiyuan Huang, Toby Maher, Dinesh Khanna
Summary: This study aimed to establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). The results showed that using the proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time.
Article
Rheumatology
Christopher P. Denton, Nicole S. Goh, Stephen M. Humphries, Toby M. Maher, Robert Spiera, Anand Devaraj, Lawrence Ho, Christian Stock, Elvira Erhardt, Margarida Alves, Athol U. Wells
Summary: Data from the SENSCIS trial suggests that patients with SSc-ILD are at risk of ILD progression and can benefit from nintedanib regardless of the extent of fibrotic ILD at baseline.
Article
Rheumatology
Lan Yu, Robyn T. Domsic, Lesley-Ann Saketkoo, Jane Withey, Tracy M. Frech, Ariane L. Herrick, Laura K. Hummers, Ami A. Shah, Christopher P. Denton, Dinesh Khanna, John D. Pauling
Summary: A novel patient-reported outcome instrument, the ASRAP questionnaire, has been developed and scored to assess the severity and impact of RP in SSc. The questionnaire was developed with extensive patient input and went through qualitative assessment and linguistic testing. A long-form and short-form version of the ASRAP questionnaire have been calibrated and scored for formal validation.
ARTHRITIS CARE & RESEARCH
(2023)
Article
Rheumatology
Sheena Ramyead, Christopher P. Denton, Catherine H. Orteu, Victoria Swale, Jorge Mayor-Jerez, Emma Gardette
Summary: We present a case of angiosarcoma in a patient with anti-U3 ribonucleoprotein antibody-positive systemic sclerosis. The angiosarcoma presented as an enlarging purple plaque on the non-sclerotic skin. This is the first reported case of angiosarcoma arising from non-sclerotic skin in systemic sclerosis patients. Clinicians should be vigilant for atypical vascular tumors in patients with systemic sclerosis.
JOURNAL OF SCLERODERMA AND RELATED DISORDERS
(2023)
Article
Rheumatology
Carolina Teles, Chiranthi Kongala Liyanage, Geoffrey Chow, Christopher P. Denton, Voon Ong
Summary: This case report presents a 63-year-old female patient with relapsing polychondritis mimicking systemic sclerosis progression, highlighting the challenging features and emphasizing the importance of early diagnosis and prompt management. The case also sheds light on the complex interplay between these two diseases and vasculitic mechanisms.
JOURNAL OF SCLERODERMA AND RELATED DISORDERS
(2023)
Article
Rheumatology
Yannick Allanore, Dinesh Khanna, Vanessa Smith, Martin Aringer, Anna-Maria Hoffmann-Vold, MasatakaKuwana Kuwana, Peter A. Merkel, Christian Stock, Steven Sambevsk, Christopher P. Denton
Summary: This study investigates the course of interstitial lung disease (ILD) in patients with limited cutaneous systemic sclerosis (lcSSc) and the effects of nintedanib. The results indicate that nintedanib can slow the decline in lung function in these patients.
Review
Rheumatology
Laura Ross, Nancy Maltez, Michael Hughes, Jan W. Schoones, Murray Baron, Lorinda Chung, Dilia Giuggioli, Pia Moinzadeh, Yossra A. Suliman, Corrado Campochiaro, Yannick Allanore, Christopher P. Denton, Oliver Distler, Tracy Frech, Daniel E. Furst, Dinesh Khanna, Thomas Krieg, Masataka Kuwana, Marco Matucci-Cerinic, Janet Pope, Alessia Alunno
Summary: A systematic literature review found that intravenous iloprost, phosphodiesterase-5 inhibitors, and atorvastatin are effective for the treatment of SSc digital ulcers. Bosentan can reduce the occurrence of future ulcers. Limited evidence supports the effectiveness of Janus kinase inhibitors, while immunosuppression or anti-platelet agents have insufficient data to support their use. Further research is needed to define the optimal treatment regimen.
Article
Rheumatology
Ivan Foeldvari, Kathryn S. Torok, Jordi Anton, Michael Blakley, Tamas Constantin, Megan Curran, Maurizio Cutolo, Christopher Denton, Kim Fligelstone, Francesca Ingegnoli, Suzanne C. Li, Dana Nemcova, Catherine Orteu, Clarissa Pilkington, Vanessa Smith, Anne Stevens, Jens Klotsche, Dinesh Khanna, Patricia Costa-Reis, Francesco Del Galdo, Bernd Hinrichs, Ozgur Kasapcopur, Clare Pain, Nicolino Ruperto, Alison Zheng, Daniel E. Furst
Summary: This study aims to define appropriate outcomes for juvenile systemic sclerosis (SSc) in order to develop successful treatment strategies. Through consensus meetings and data analysis, multiple domains including global disease activity, skin condition, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, gastrointestinal involvement, and quality of life were agreed upon as evaluation measures. Rating: 8/10.
ARTHRITIS CARE & RESEARCH
(2023)
Article
Rheumatology
Dinesh Khanna, Christopher P. Denton, Daniel E. Furst, Maureen D. Mayes, Marco Matucci-Cerinic, Vanessa Smith, Dick de Vries, Paul Ford, Yasmina Bauer, Matthew J. Randall, Mitra Ebrahimpoor, Laszlo Kupcsik, Pieter-Jan Stiers, Liesbeth Deberdt, Niyati Prasad, Sharlene Lim, Philippe Pujuguet, Sohail Ahmed
Summary: The study aimed to investigate the efficacy, safety, and tolerability of ziritaxestat in patients with early dcSSc. The results showed that ziritaxestat significantly reduced the modified Rodnan skin score compared to placebo and was well tolerated. Biomarker analysis suggested that ziritaxestat may reduce fibrosis. In conclusion, this study highlights the importance of ziritaxestat in improving skin involvement in patients with dcSSc.
ARTHRITIS & RHEUMATOLOGY
(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
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)
Article
Rheumatology
Yumiko L. Vreeburg, Daniel S. Knight, John G. Coghlan, Voon H. Ong, Christopher P. Denton
Summary: Systemic sclerosis, an autoimmune disease characterized by fibrosis and small vessel vasculopathy, can affect various organ systems, including the heart. Takotsubo cardiomyopathy is a transient cardiomyopathy that occurs in response to emotional or physical triggers. This study identified five female patients with systemic sclerosis who were diagnosed with Takotsubo cardiomyopathy, and some of them had recurrent episodes. The findings suggest a potential association between systemic sclerosis and Takotsubo cardiomyopathy.
JOURNAL OF SCLERODERMA AND RELATED DISORDERS
(2023)
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)