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
Biochemistry & Molecular Biology
Mor Zaaroor Levy, Noa Rabinowicz, Maia Yamila Kohon, Avshalom Shalom, Ariel Berl, Tzipi Hornik-Lurie, Liat Drucker, Shelly Tartakover Matalon, Yair Levy
Summary: miR-26 and miR-let-7d may be serological markers for SSc-PAH and are involved in myofibroblast differentiation and complement pathway activation.
Article
Medicine, General & Internal
Hirohito Kotani, Ayumi Yoshizaki, Kazuki M. Matsuda, Yuta Norimatsu, Ai Kuzumi, Maiko Fukayama, Takemichi Fukasawa, Satoshi Ebata, Asako Yoshizaki-Ogawa, Yoshihide Asano, Koji Oba, Shinichi Sato
Summary: Systemic sclerosis (SSc) patients have significantly higher serum calponin 3 levels compared to healthy controls, with the high level group showing increased skin thickness scores and a higher frequency of joint pain. Serum calponin 3 levels may serve as a biomarker for the severity of skin sclerosis and joint involvement in SSc.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Devis Benfaremo, Silvia Agarbati, Matteo Mozzicafreddo, Chiara Paolini, Silvia Svegliati, Gianluca Moroncini
Summary: Systemic sclerosis, also known as scleroderma or SSc, is a highly varied disease in terms of clinical presentation, disease progression, and treatment response. Recent advancements in skin molecular profiling technologies have enabled the identification of patient subgroups based on gene expression analysis. This narrative review provides an overview of the current status of skin gene expression analysis and emphasizes the benefits of stratifying patients based on their gene signatures. This stratification has the potential to lead to a precision medicine approach in the management of SSc.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Rheumatology
Gabriela Riemekasten, Joerg H. W. Distler
Summary: This article focuses on the pathogenesis and treatment of SSc, discussing the contribution of environmental factors and regulatory autoantibodies. It also explores the role of fibroblasts, nuclear receptors, and epigenetic modifications in SSc. Additionally, it highlights the potential of pharmacological interventions for pathological signaling.
THERAPEUTIC ADVANCES IN MUSCULOSKELETAL DISEASE
(2022)
Article
Medicine, General & Internal
Yehya Al-Adwi, Isabella Maria Atzeni, Berber Doornbos-van der Meer, Marcel John van der Leij, Rita Delphine Maiko Varkevisser, Alja Stel, Wim Timens, Christiaan Tji Gan, Harry van Goor, Johanna Westra, Douwe Johannes Mulder
Summary: This study assessed the use of CXCL10 as a predictive biomarker for new onset of SSc-ILD. The findings showed that serum CXCL10 levels were higher in SSc-ILD patients compared to SSc patients without ILD. Survival analysis indicated that baseline CXCL10 levels >78.5 pg/ml had a 2.74-fold increased risk of developing new onset of ILD.
Article
Immunology
Lamia Khan, Tahlia Derksen, Desiree Redmond, Jan Storek, Caylib Durand, Robert Gniadecki, Benjamin Korman, Jan Willem Cohen Tervaert, Ana D'Aubeterre, Mohammed S. Osman, Lisa M. Willis
Summary: This study found that polySia is dysregulated in patients with systemic sclerosis (SSc) and correlates with the degree of skin fibrosis. The aberrant expression of polySia highlights its potential use as a biomarker in patients with progressive forms of SSc. Dysregulated polySia levels in SSc further emphasizes the cancer-like phenotype present in SSc, which may promote fibrosis and immune dysregulation.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Biochemistry & Molecular Biology
Iulia Szabo, Laura Muntean, Tania Crisan, Voicu Rednic, Claudia Sirbe, Simona Rednic
Summary: Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes characterized by microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms and miRNAs play crucial roles in SSc pathogenesis, offering potential as biomarkers and therapeutic targets.
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.
Review
Cell Biology
Amila Iriskic Atic, Maja Thiele, Alexander Munk, Louise Torp Dalgaard
Summary: MicroRNAs (miRNAs) secreted by the liver have the potential to be important biomarkers for nonalcoholic liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Several miRNAs, including miR-122, miR-21, miR-34a, miR-192, miR-193, and the miR-17-92 miRNA-cluster, are consistently associated with NAFLD/NASH. These miRNAs show potential as diagnostic markers for NAFLD/NASH, although more research is needed to understand their specificity and regulation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
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
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
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
Medicine, General & Internal
Xi Xie, Haina Gan, Jing Tian, Fen li, Jinwei Chen, Jia Wang, Jiafeng Liao, Shu Li
Summary: T-614 inhibited dermal fibroblasts activation and skin fibrosis in experimental SSc models by regulating TGF-beta 1/smad pathway.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, General & Internal
Zhanying Hou, Xuehan Su, Guangming Han, Ruzeng Xue, Yangxia Chen, Ye Chen, Huan Wang, Bin Yang, Yunsheng Liang, Suyun Ji
Summary: This study found that JAK1 and JAK2 inhibitors have significant efficacy in alleviating skin fibrosis and digital ulcers in systemic sclerosis (SSc) patients. Baricitinib, an oral JAK1/2 inhibitor, is a potentially effective treatment for SSc patients with skin fibrosis and ulcers, with good tolerability. Further large-scale clinical trials are needed to confirm these preliminary findings.
FRONTIERS IN MEDICINE
(2022)
Article
Immunology
Sandra C. Silva-Cardoso, Alsya J. Affandi, Lotte Spel, Marta Cossu, Joel A. G. van Roon, Marianne Boes, Timothy R. D. J. Radstake
JOURNAL OF IMMUNOLOGY
(2017)
Article
Immunology
Alsya J. Affandi, Sandra C. Silva-Cardoso, Samuel Garcia, Emmerik F. A. Leijten, Tessa S. van Kempen, Wioleta Marut, Joel A. G. van Roon, Timothy R. D. J. Radstake
EUROPEAN JOURNAL OF IMMUNOLOGY
(2018)
Article
Immunology
Alsya J. Affandi, Tiago Carvalheiro, Timothy R. D. J. Radstake, Wioleta Marut
IMMUNOLOGY LETTERS
(2018)
Article
Immunology
Eleni Chouri, Nila H. Servaas, Cornelis P. J. Bekker, Alsya J. Affandi, Marta Cossu, Maarten R. Hillen, Chiara Angiolilli, Jorre S. Mertens, Lucas L. van den Hoogen, Sandra Silva-Cardoso, Maarten van der Kroef, Nadia Vazirpanah, Catharina G. K. Wichers, Tiago Carvalheiro, Sofie L. M. Blokland, Barbara Giovannone, Laura Porretti, Wioleta Marut, Barbara Vigone, Joel A. G. van Roon, Lorenzo Beretta, Marzia Rossato, Timothy R. D. J. Radstake
JOURNAL OF AUTOIMMUNITY
(2018)
Review
Immunology
Joanna Grabowska, Miguel A. Lopez-Venegas, Alsya J. Affandi, Joke M. M. den Haan
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Rheumatology
Maarten van der Kroef, Monica Castellucci, Michal Mokry, Marta Cossu, Marianna Garonzi, Lara M. Bossini-Castillo, Eleni Chouri, Catharina G. K. Wichers, Lorenzo Beretta, Elena Trombetta, Sandra Silva-Cardoso, Nadia Vazirpanah, Tiago Carvalheiro, Chiara Angiolilli, Cornelis P. J. Bekker, Alsya J. Affandi, Kris A. Reedquist, Femke Bonte-Mineur, Els J. M. Zirkzee, Flavia Bazzoni, Timothy R. D. J. Radstake, Marzia Rossato
ANNALS OF THE RHEUMATIC DISEASES
(2019)
Article
Rheumatology
Alsya J. Affandi, Tiago Carvalheiro, Andrea Ottria, Jasper C. A. Broen, Lara Bossini-Castillo, Ralph G. Tieland, Lenny van Bon, Eleni Chouri, Marzia Rossato, Jorre S. Mertens, Samuel Garcia, Aridaman Pandit, Laurie M. G. de Kroon, Romy B. Christmann, Javier Martin, Joel A. G. van Roon, Timothy R. D. J. Radstake, Wioleta Marut
ANNALS OF THE RHEUMATIC DISEASES
(2019)
Article
Rheumatology
Tiago Carvalheiro, Alsya J. Affandi, Beatriz Malvar-Fernandez, Ilse Dullemond, Marta Cossu, Andrea Ottria, Jorre S. Mertens, Barbara Giovannone, Femke Bonte-Mineur, Marc R. Kok, Wioleta Marut, Kris A. Reedquist, Timothy R. Radstake, Samuel Garcia
ARTHRITIS & RHEUMATOLOGY
(2019)
Article
Immunology
Maarten van der Kroef, Lucas L. van den Hoogen, Jorre S. Mertens, Sofie L. M. Blokland, Scott Haskett, Abhinandan Devaprasad, Tiago Carvalheiro, Eleni Chouri, Nadia Vazirpanah, Marta Cossu, Catherina G. K. Wichers, Sandra C. Silva-Cardoso, Alsya J. Affandi, Cornelis P. J. Bekker, Ana P. Lopes, Maarten R. Hillen, Femke Bonte-Mineur, Marc R. Kok, Lorenzo Beretta, Marzia Rossato, Michael Mingueneau, Joel A. G. van Roon, Timothy R. D. J. Radstake
EUROPEAN JOURNAL OF IMMUNOLOGY
(2020)
Article
Multidisciplinary Sciences
Alsya J. Affandi, Joanna Grabowska, Katarzyna Olesek, Miguel Lopez Venegas, Arnaud Barbaria, Ernesto Rodriguez, Patrick P. G. Mulder, Helen J. Pijffers, Martino Ambrosini, Hakan Kalay, Tom O'Toole, Eline S. Zwart, Geert Kazemier, Kamran Nazmi, Floris J. Bikker, Johannes Stoeckl, Alfons J. M. van den Eertwegh, Tanja D. de Gruijl, Gert Storm, Yvette van Kooyk, Joke M. M. den Haan
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Chemistry, Multidisciplinary
J. Grabowska, A. J. Affandi, D. van Dinther, M. K. Nijen Twilhaar, K. Olesek, L. Hoogterp, M. Ambrosini, D. A. M. Heijnen, L. Klaase, A. Hidalgo, K. Asano, P. R. Crocker, G. Storm, Y. van Kooyk, J. M. M. den Haan
Summary: In this study, liposomes containing GM3 were shown to efficiently target CD169(+) macrophages, inducing specific immune responses including antigen-specific CD8(+) and CD4(+) T cell as well as B cell responses. Administration of GM3 liposomes containing ovalbumin resulted in delayed tumor growth and improved survival in B16-OVA tumor bearing mice. The study also highlighted the essential role of CD169(+) macrophages and cDC1s in inducing CD8(+) T cell immunity through liposomal vaccination.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Pharmacology & Pharmacy
Maarten K. Nijen Twilhaar, Lucas Czentner, Joanna Grabowska, Alsya J. Affandi, Chun Yin Jerry Lau, Katarzyna Olesek, Hakan Kalay, Cornelus F. van Nostrum, Yvette van Kooyk, Gert Storm, Joke M. M. den Haan
Article
Immunology
N. H. Servaas, F. Zaaraoui-Boutahar, C. G. K. Wichers, A. Ottria, E. Chouri, A. J. Affandi, S. Silva-Cardoso, M. van der Kroef, T. Carvalheiro, F. van Wijk, T. R. D. J. Radstake, A. C. Andeweg, A. Pandit
Summary: The study shows that CD4(+) and CD8(+) T-cell receptors in Systemic Sclerosis (SSc) patients are highly persistent over time, likely due to antigen selection. Persistent T-cell receptors form clusters with other sequences that potentially recognize the same antigens, supporting antigen-driven expansion of CD4(+)/CD8(+) T-cells in SSc.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Medicine, General & Internal
Eleni Chouri, Maojie Wang, Maarten R. Hillen, Chiara Angiolilli, Sandra C. Silva-Cardoso, Catharina G. K. Wichers, Maarten van der Kroef, Cornelis P. J. Bekker, Marta Cossu, Lenny van Bon, Alsya J. Affandi, Tiago Carvalheiro, Aridaman Pandit, Joel A. G. van Roon, Lorenzo Beretta, Boudewijn M. T. Burgering, Timothy R. D. J. Radstake, Marzia Rossato
Summary: The study found that miRNA expression levels are altered in pDCs of early-stage SSc patients and may contribute to the observed pDC activation in patients.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Immunology
Alsya J. Affandi, Katarzyna Olesek, Joanna Grabowska, Maarten K. Nijen Twilhaar, Ernesto Rodriguez, Anno Saris, Eline S. Zwart, Esther J. Nossent, Hakan Kalay, Michael de Kok, Geert Kazemier, Johannes Stockl, Alfons J. M. van den Eertwegh, Tanja D. de Gruijl, Juan J. Garcia-Vallejo, Gert Storm, Yvette van Kooyk, Joke M. M. den Haan
Summary: CD169(+) monocytes are activated monocytes with enhanced capacity to stimulate CD8(+) T cells. They are present in various diseases, including viral infections and cancers, and emerge as an interesting target in nanovaccine strategies. The study also showed that two CD169-targeting nanovaccine platforms efficiently presented tumor-associated peptides to antigen-specific CD8(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2021)