Review
Immunology
Satoka Shiratori-Aso, Daigo Nakazawa
Summary: AAV is a serious autoimmune disease characterized by vascular necrosis. The pathogenesis involves ANCA-mediated neutrophil activation, NETs formation, and a vicious cycle of NETs and ANCA production. Understanding the molecular signaling pathways in aberrant neutrophil activation and NETs clearance systems may lead to specific therapeutics for AAV. Standard therapy with glucocorticoids and immunosuppressants has improved outcomes, but targeted therapies for neutrophil activation and NETs clearance are potential alternatives.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Rheumatology
Stavros Giaglis, Douglas Daoudlarian, Jens Thiel, Marta Rizzi, Diego Kyburz, Nils Venhoff, Ulrich A. Walker
Summary: This study aims to investigate the level and nature of circulating DNA in ANCA-associated vasculitis (AAV) and evaluate the clinical utility of DNA quantification. It was found that mtDNA, but not nDNA, is elevated in the plasma of AAV patients and correlated with disease activity. mtDNA quantification could be a superior biomarker in the laboratory monitoring of AAV activity.
Correction
Hematology
S. Sangaletti, C. Tripodo, C. Chiodoni
Summary: This study demonstrates that the structures of NETs are highly immunogenic to trigger an adaptive immune response relevant for autoimmunity.
Article
Medicine, General & Internal
Borros Arneth, Rebekka Arneth
Summary: Research has shown that NETs contribute to the pathogenesis of vasculitis through different mechanisms, including renal failure and vascular damage. The protective effects of NETs have also been highlighted. However, the role of neutrophil hyperactivity in vasculitis is not fully understood. More studies are needed to determine the accurate function of NETs in vasculitis pathogenesis.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Immunology
Xiu-Qi Chen, Li Tu, Jia-Sen Zou, Shi-Qun Zhu, Yan-Jun Zhao, Yuan-Han Qin
Summary: The study aimed to investigate the involvement of neutrophil extracellular traps (NETs) in the pathogenesis of IgA vasculitis (IgAV) and their association with disease activity in children. Circulating levels of cf-DNA, MPO-DNA, and NE were significantly higher in onset and active IgAV patients compared to remission, drug withdrawal patients, and healthy controls. Our data suggest that NETs are released into the circulation of IgAV patients and may be used as a marker to assess disease severity in children with IgAV.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Rheumatology
Durga Prasanna Misra, Koshy Nithin Thomas, Armen Yuri Gasparyan, Olena Zimba
Summary: Patients with AAV have an increased risk of developing venous and arterial thrombotic events due to endothelial injury caused by neutrophil activation and NETs expression. Additionally, APLs and anti-plasminogen antibodies further contribute to thrombosis in AAV.
CLINICAL RHEUMATOLOGY
(2021)
Article
Cell Biology
Hidehito Kimura, Akiko Mii, Jun Shoji, Yusuke Arakawa, Akira Shimizu
Summary: This study investigated the relationship between infiltrating citrullinated histone H3 (H3Cit)-positive neutrophils and disease specificity and activity in various glomerulonephritides. The presence of H3Cit+ neutrophils was found to be a potential marker for disease activity in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).
Review
Immunology
Xiu-Qi Chen, Li Tu, Qing Tang, Li Huang, Yuan-Han Qin
Summary: IgA vasculitis is the most common systemic small vessel vasculitis in childhood. Its pathogenesis may be related to various factors such as genetics, infection, environment, and drugs. The presence of neutrophil extracellular traps (NETs) is associated with disease activity.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Oncology
Phei Er Saw, Jianing Chen, Erwei Song
Summary: Neutrophil extracellular traps (NETs) are involved in both infection control and tumor metastasis. The study by Mousset et al. published in Cancer Cell reveals that chemotherapy-induced inflammation promotes NETosis in malignant tumors, leading to chemoresistance. This finding highlights the potential of targeting inflammatory NETs for cancer treatment.
Review
Immunology
Yuji Nozaki
Summary: Biologics targeting inflammation-related molecules have revolutionized the treatment of rheumatoid arthritis and ANCA-associated vasculitis. However, challenges remain in treating vasculitis effectively. New drugs in clinical trials offer promising options for vasculitis treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Iwona Wojcik, Manfred Wuhrer, Peter Heeringa, Coen A. Stegeman, Abraham Rutgers, David Falck
Summary: This study found that the glycosylation changes of IgG are associated with disease flares in patients with ANCA-associated vasculitis. In addition, among the glycosylation changes, alterations in Fc bisection and fucosylation levels of IgG are correlated with long-term treatment outcome and impending relapse.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Marilia A. Dagostin, Sergio L. O. Nunes, Samuel K. Shinjo, Rosa M. R. Pereira
Summary: The mortality rate of patients with anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) in Brazil is higher than the general population. In Brazilian patients, mortality is associated with high damage index, renal impairment, and CRP levels.
Article
Multidisciplinary Sciences
Hannes A. Baukmann, Justin L. Cope, Colin Bannard, Alexander R. E. C. Schwinges, Margaretha R. J. Lamparter, Sarah Groves, Charles N. J. Ravarani, Borko Amulic, Joern E. Klinger, Marco F. Schmidt
Summary: Despite the availability of vaccines to prevent SARS-CoV-2 infection, treating critically ill COVID-19 patients remains crucial. This study presents an alternative method for identifying drug repurposing targets by screening disease-causing traits, leading to the discovery of potential treatment targets for critical illness.
Review
Medicine, General & Internal
Salem Almaani, Lynn A. Fussner, Sergey Brodsky, Alexa S. Meara, David Jayne
Summary: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of small vessel vasculitides characterized by granulomatous and neutrophilic tissue inflammation, often associated with the production of antibodies that target neutrophil antigens. AAV involves multiple organ systems clinically, including the lungs, kidneys, skin, and nervous system. The prognosis of AAV has significantly improved due to advances in understanding its pathogenesis and treatment options.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Fumin Qi, Jian Hao, Wei Wei
Summary: According to the study, the different ANCA serotypes in Chinese AAV patients have no impact on the likelihood of induced remission, patient survival, or disease recurrence. Younger patients with milder kidney involvement and lower disease assessment scores tend to have a better prognosis.
ANNALS OF MEDICINE
(2023)
Article
Rheumatology
Alexandru Garaiman, Klaus Steigmiller, Catherine Gebhard, Carina Mihai, Rucsandra Dobrota, Cosimo Bruni, Marco Matucci-Cerinic, Joerg Henes, Jeska De Vries-Bouwstra, Vanessa Smith, Andrea Doria, Yannick Allanore, Lorenzo Dagna, Branimir Anic, Carlomaurizio Montecucco, Otylia Kowal-Bielecka, Mickael Martin, Yoshiya Tanaka, Anna-Maria Hoffmann-Vold, Ulrike Held, Oliver Distler, Mike Oliver Becker
Summary: The DU-VASC model was developed and validated to assist in decision-making for the management of digital ulcers in patients with systemic sclerosis. The model showed that PI treatment was the most important predictor associated with reduced occurrence of digital ulcers.
Article
Rheumatology
Cristina Arriens, Y. K. Onno Teng, Ellen M. Ginzler, Samir V. Parikh, Anca D. Askanase, Amit Saxena, Keisha Gibson, Dawn J. Caster, Tatsuya Atsumi, Laura Lisk, Simrat Randhawa, Rashieda Gluck, Neil Solomons, Robert B. Huizinga
Summary: This integrated analysis evaluates the efficacy and safety of voclosporin in the treatment of lupus nephritis. The study found that voclosporin, in combination with mycophenolate mofetil and oral glucocorticoids, significantly improved renal response compared to control, with similar incidence of adverse events. The results confirm the effectiveness and safety of voclosporin across diverse racial and ethnic groups.
ARTHRITIS CARE & RESEARCH
(2023)
Article
Rheumatology
Luuk Wieske, Eileen W. Stalman, P. J. Koos van Dam, Laura Y. Kummer, Maurice Steenhuis, Zoe L. E. van Kempen, Joep Killestein, Adriaan G. Volkers, Sander W. Tas, Laura Boekel, Gertjan Wolbink, Anneke van der Kooi, Joost Raaphorst, Mark Lowenberg, Bart Takkenberg, Geert R. A. M. D'Haens, Phyllis Spuls, Marcel W. Bekkenk, Annelie H. Musters, Nicoline F. Post, Angela L. Bosma, Marc L. Hilhorst, Yosta Vegting, Frederique J. Bemelman, Alexandre Voskuyl, Bo Broens, Agner Parra Sanchez, Cecile A. C. M. van Els, Jelle De Wit, Abraham Rutgers, Karina de Leeuw, Barbara Horvath, Jan J. G. M. Verschuuren, Annabel M. Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Cornelia F. Allaart, Y. K. Onno Teng, Pieter van Paassen, Matthias H. Busch, Papay B. P. Jallah, Esther Brusse, Pieter A. van Doorn, Adaja Elisabeth Baars, Dirkjan Hijnen, Corine R. G. Schreurs, W. Ludo Van der Pol, H. Stephan Goedee, Sofie Keijzer, Jim Keijser, Olvi Cristianawati, Anja ten Brinke, Niels J. M. Verstegen, Koos A. H. Zwinderman, S. Marieke van Ham, Taco W. Kuijpers, Theo Rispens, Filip Eftimov
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Rheumatology
Theresa Kissel, Rene E. M. Toes, Thomas W. J. Huizinga, Manfred Wuhrer
Summary: Glycosylation is a common modification that affects protein stability and interactions. It plays a significant role in rheumatic diseases, influencing inflammatory processes and disease progression. Understanding the impact of glycosylation on plasma proteins, cells, and tissues opens up potential interventions for the treatment of these diseases.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Rheumatology
Bernhard Hellmich, Beatriz Sanchez-Alamo, Jan H. Schirmer, Alvise Berti, Daniel Blockmans, Maria C. Cid, Julia U. Holle, Nicole Hollinger, Omer Karadag, Andreas Kronbichler, Mark A. Little, Raashid A. Luqmani, Alfred Mahr, Peter A. Merkel, Aladdin J. Mohammad, Sara Monti, Chetan B. Mukhtyar, Jacek Musial, Fiona Price-Kuehne, Marten Segelmark, Y. K. Onno Teng, Benjamin Terrier, Gunnar Tomasson, Augusto Vaglio, Dimitrios Vassilopoulos, Peter Verhoeven, David Jayne
Summary: Since the publication of the EULAR recommendations for the management of AAV in 2016, several clinical trials have been conducted that have the potential to change clinical care. A systematic literature review and expert opinions were used to modify existing recommendations and create new ones. The recommendations provide updated guidance on AAV management.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Rheumatology
Chi Chiu Mok, Y. K. Onno Teng, Ramesh Saxena, Yoshiya Tanaka
Summary: In systemic lupus erythematosus, kidney involvement known as lupus nephritis is a serious condition with limited treatment options. This review analyzes current management guidelines, discusses emerging therapies, and explores the potential for precision medicine in treating lupus nephritis. Despite advancements, the prognosis for lupus nephritis has not significantly improved, and there are variations in treatment recommendations due to inter-ethnic differences and lack of evidence. New treatments and investigational drugs, such as calcineurin inhibitors and biologic agents, offer hope for improved outcomes. Molecular profiling and urine proteomic panels may help personalize treatment in the future.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Mathematics, Applied
Yuankai Teng, Zhu Wang, Lili Ju, Anthony Gruber, Guannan Zhang
Summary: Due to the challenge of dimensionality and limited training data, approximating high-dimensional functions is a difficult task. This paper introduces a new method called Dimension Reduction via Learning Level Sets (DRiLLS) for function approximation. The method uses a pseudoreversible neural network (PRNN) module to transform high-dimensional inputs to low-dimensional active variables, and a synthesized regression module to approximate function values in the low-dimensional space. Experimental results show that DRiLLS outperforms other methods, especially for target functions with critical points.
SIAM JOURNAL ON SCIENTIFIC COMPUTING
(2023)
Letter
Rheumatology
Tineke J. van Wesemael, Sanne Reijm, Atsushi Kawakami, Annemarie L. Dorjee, Gerrie Stoeken, Takahiro Maeda, Shin-ya Kawashiri, Tom W. J. Huizinga, Mami Tamai, Rene E. M. Toes, Diane van der Woude
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Miles D. Holborough-Kerkvliet, Sanne Kroos, Renee van de Wetering, Rene E. M. Toes
Summary: Autoimmune diseases are characterized by a breakdown of immunological tolerance to self, resulting in an abnormal immune response to self-antigens. The pathogenesis is driven by a complex interaction between autoreactive B and T cells. B cell targeting therapies, such as Rituximab, have shown efficacy in reducing symptoms of autoimmune diseases, but can also lead to infections. Therefore, antigen-specific approaches to target autoreactive cells are being investigated.
IMMUNOLOGY LETTERS
(2023)
Article
Medicine, Research & Experimental
Sanne Reijm, Joanneke C. Kwekkeboom, Nienke J. Blomberg, Jolien Suurmond, Diane van der Woude, Rene E. M. Toes, Hans U. Scherer
Summary: This study visualizes the B cell response against posttranslational modification antigens in autoimmune diseases. The results demonstrate extensive cross-reactivity of B cells against different antigens and the presence of PTM-directed plasmablasts in patients. The expression of CXCR3 suggests the potential involvement of chemokines in this process.
Article
Rheumatology
Corrie M. Wortel, Sophie I. E. Liem, Nina M. van Leeuwen, Maaike Boonstra, Cynthia M. Fehres, Lauran Stoeger, Tom W. J. Huizinga, Rene E. M. Toes, Jeska De Vries-Bouwstra, Hans U. Scherer
Summary: This study investigates the autoreactive B cell responses in ATA-positive and ACA-positive SSc patients. The results show that ATA-positive patients exhibit a more active B cell response, which is associated with the presence and severity of ILD. This may explain the differential responsiveness to B cell depleting therapy.
Article
Rheumatology
Sophie I. E. Liem, E. M. Hoekstra, E. W. Nivine Levarht, Annemarie L. Dorjee, Hans U. Scherer, Rene E. M. Toes, Tom W. J. Huizinga, Jeska K. de Vries-Bouwstra, Cynthia M. Fehres
Summary: This study investigated the presence of different isotypes of anti-carbamylated protein (CarP) antibodies in systemic sclerosis (SSc) patients and its association with skin involvement. The results showed a higher prevalence of anti-CarP IgG in SSc patients compared to healthy controls, but no significant difference in the prevalence of IgA and IgM. Additionally, there was no significant correlation between the levels of anti-CarP antibodies and age or skin involvement.
ARTHRITIS RESEARCH & THERAPY
(2023)
Letter
Urology & Nephrology
Jolijn R. van Leeuwen, Ton J. Rabelink, Y. K. Onno Teng
KIDNEY INTERNATIONAL REPORTS
(2023)
Article
Medicine, Research & Experimental
Jolijn R. van Leeuwen, Tamara Popov, Achim Obergfell, Ton J. Rabelink, Y. K. Onno Teng
BIOLOGICS-TARGETS & THERAPY
(2023)
