Article
Immunology
Morten Aagaard Nielsen, Kristian Juul-Madsen, John Stegmayr, Chao Gao, Akul Y. Mehta, Stinne Ravn Greisen, Tue Wenzel Kragstrup, Malene Hvid, Thomas Vorup-Jensen, Richard D. Cummings, Hakon Leffler, Bent Winding Deleuran
Summary: The study shows that Gal-3 binds to 4-1BB and forms large soluble 4-1BB/Gal-3 complexes that attach to mem4-1BB on the cell surfaces, leading to suppression of 4-1BBL's bioactivity. In rheumatoid arthritis patients, the complexes containing 4-1BB/Gal-3 were significantly reduced.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Yu Sun, Haoran Hu, Zheng Liu, Jian Xu, Yiyun Gao, Xinyu Zhan, Shun Zhou, Weizhe Zhong, Dongming Wu, Ping Wang, Zhuqing Rao, Lianbao Kong, Haoming Zhou
Summary: The role and mechanism of macrophage STING signaling in modulating tumor microenvironment to suppress tumor growth at secondary sites remains largely unclear.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Hematology
Julian Swatler, Laura Turos-Korgul, Marta Brewinska-Olchowik, Sara De Biasi, Wioleta Dudka, Bac Viet Le, Agata Kominek, Salwador Cyranowski, Paulina Pilanc, Elyas Mohammadi, Dominik Cysewski, Ewa Kozlowska, Wioleta Grabowska-Pyrzewicz, Urszula Wojda, Grzegorz Basak, Jakub Mieczkowski, Tomasz Skorski, Andrea Cossarizza, Katarzyna Piwocka
Summary: Leukemic extracellular vesicles play a role in stimulating immunosuppressive Tregs and promoting leukemia growth. The study identifies Rab27a-dependent secretion of leukemic EVs as a potential therapeutic target in myeloid neoplasms.
Article
Pharmacology & Pharmacy
Cullen M. Lilley, Andrea Alarcon, My-Huyen Ngo, Jackeline S. Araujo, Luis Marrero, Kimberlee S. Mix
Summary: The orphan nuclear receptor 4A2 (NR4A2/Nurr1) plays an important role in the development of rheumatoid arthritis (RA) and is overexpressed in inflamed synovium. The expression of NR4A2 and its upstream regulator, nuclear factor kappa B (NF-kappa B), increases during disease progression, early expressed in inflamed synovium. Screening of RA-related genes revealed that NR4A receptors and NF-kappa B-1 play central regulatory roles in this model.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Marwa M. Qadri
Summary: Rheumatoid arthritis, osteoarthritis, and gout are common joint diseases with unclear pathogenesis. CD44 and its variants play a key role in joint damage and inflammation, suggesting that targeting CD44 could be a promising treatment strategy. PRG4 is a mucinous glycoprotein involved in joint lubrication, and lack of PRG4 expression leads to chronic inflammation and fibrosis. This review summarizes the role of PRG4-CD44 signaling in controlling synovitis, synovial hypertrophy, and tissue fibrosis in DJDs.
Article
Biochemistry & Molecular Biology
Daqian Wan, Songtao Ai, Huoniu Ouyang, Liming Cheng
Summary: Senile osteoporosis, affecting the elderly population, is caused by abnormal changes in bone marrow stromal cells and signaling pathways in the bone marrow microenvironment. Elevated levels of 4-1BB in aged mice inhibit osteogenic differentiation, leading to bone loss, which can be rescued by blocking the 4-1BB signaling pathway. These findings suggest a potential therapeutic target for age-related trabecular bone loss.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Medicine, General & Internal
Gabriela Athziri Sanchez-Zuno, Richard Bucala, Jorge Hernandez-Bello, Ilce Valeria Roman-Fernandez, Mariel Garcia-Chagollan, Ferdinando Nicoletti, Monica Guadalupe Matuz-Flores, Samuel Garcia-Arellano, Judith Alejandra Esparza-Michel, Sergio Cerpa-Cruz, Edsaul Emilio Perez-Guerrero, Jose Francisco Munoz-Valle
Summary: Macrophage migration inhibitory factor (MIF) plays a significant role in the pathogenesis of rheumatoid arthritis (RA). This study explored the expression of CD74, CXCR2, CXCR4, and CXCR7, as well as the levels of soluble CD74 (sCD74), in relation to the clinical activity of RA. The results suggest that sCD74 may act as a decoy receptor for MIF and negatively regulate its signaling, while CXCR7 functions as a scavenger-type receptor to prevent endocytosis and degradation of CXCR4 under inflammatory conditions.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Rheumatology
Jonathan Aldridge, Kerstin Andersson, Inger Gjertsson, Anna-Karin Hultgard Ekwall, Magnus Hallstrom, Ronald van Vollenhoven, Anna-Carin Lundell, Anna Rudin
Summary: This study found that the proportions of PD-1(+)TFh and CTLA-4(+) conventional CD4(+) T cells in circulation at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.
Article
Rheumatology
D. Bertrand, V Stouten, D. De Cock, S. Pazmino, M. Doumen, I de Wergifosse, J. Joly, V Badot, L. Corluy, I Hoffman, V Taelman, K. De Knop, E. Geens, C. Langenaken, J. L. Lenaerts, J. Lenaerts, M. Walschot, J. Mannaerts, R. Westhovens, P. Verschueren
Summary: This study investigated the feasibility of tapering etanercept in patients with RA in sustained remission, finding that while non-inferiority could not be demonstrated, tapering to EOW appeared feasible. Sixty-six patients were randomized to weekly or EOW etanercept, with a higher proportion maintaining disease control in the weekly group.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2022)
Article
Immunology
Bazgha Gul, Rukhsana Anwar, Mohammad Saleem, Afifa Noor, Muhammad Ihsan Ullah
Summary: The current study evaluated the anti-arthritic activity of n-hexane and aqueous extracts of Cassia absus seeds. The extracts showed significant inhibition of paw edema and reduction in paw size and joint diameter. The extracts also improved the levels of inflammatory and oxidative biomarkers. Polymerase chain reaction investigation revealed the modulation of various inflammatory factors by the extracts. In conclusion, Cassia absus can effectively alleviate arthritis symptoms by modulating oxidative and inflammatory biomarkers.
INFLAMMOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rami M. Elshazli, Afaf M. Elsaid, Doaa M. Shawky, Lamiaa A. A. Barakat
Summary: This study found significant associations between ACE I/D and IL-4 VNTR polymorphisms with susceptibility to RA in the Egyptian population, while no association was observed with IL-1 beta G > A.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Review
Rheumatology
Tomoyuki Mutoh, Taichi Nagai, Tsuyoshi Shirai, Soshi Okazaki, Hiroko Sato, Hiroshi Fujii
Summary: This study investigated the drug survival and predictors for discontinuation of golimumab in Japanese patients with RA. The results showed that prior exposure to multiple biologics was identified as the most important factor negatively affecting the long-term retention of golimumab.
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Lobna A. Maged, Sara Saeed, Walaa Abdelfattah, Wafaa Gaber
Summary: The study aimed to investigate the utility of serum Galectin-1 (Gal-1) and Galectin-4 (Gal-4) as diagnostic markers for rheumatoid arthritis (RA) and explore their relationship with disease activity. The findings showed that Gal-1 and Gal-4 levels were significantly lower in RA patients compared to the control group, indicating their potential role as diagnostic markers for RA. However, there was no correlation between Gal-1, Gal-4, and disease activity or severity.
EGYPTIAN RHEUMATOLOGIST
(2023)
Article
Rheumatology
T. Thomsen, B. A. Esbensen, M. L. Hetland, M. Aadahl
Summary: A randomized controlled trial aimed to reduce sedentary behaviour and increase light-intensity physical activity in patients with rheumatoid arthritis. The study found that patients who are less educated and have certain types of comorbidity are less motivated to participate in physical activity interventions. The findings can help improve recruitment processes and implementation of physical activity interventions in rheumatology clinical practice.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
M. A. Nielsen, D. Koster, S. Greisen, A. Troldborg, K. Stengaard-Pedersen, P. Junker, K. Horslev-Petersen, M. L. Hetland, M. Ostergaard, M. Hvid, H. Leffler, T. W. Kragstrup, B. Deleuran
Summary: The study found that patients with rheumatoid arthritis (RA) had persistently increased levels of galectin-3 (Gal-3) in their plasma, and changes in Gal-3 levels were associated with long-term disease activity. Gal-3 levels in synovial fluid were also significantly elevated. In vitro experiments showed that a Gal-3 inhibitor could reduce the activity of inflammatory cells.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
Daniel Aletaha, Andreas Kerschbaumer, Kastriot Kastrati, Christian Dejaco, Maxime Dougados, Iain B. McInnes, Naveed Sattar, Tanja A. Stamm, Tsutomu Takeuchi, Michael Trauner, Desiree van der Heijde, Marieke Voshaar, Kevin L. Winthrop, Angelo Ravelli, Neil Betteridge, Gerd-Ruediger R. Burmester, Johannes W. J. Bijlsma, Vivian Bykerk, Roberto Caporali, Ernest H. Choy, Catalin Codreanu, Bernard Combe, Mary K. Crow, Maarten de Wit, Paul Emery, Roy M. Fleischmann, Cem Gabay, Merete Lund Hetland, Kimme L. Hyrich, Annamaria Iagnocco, John D. Isaacs, Joel M. Kremer, Xavier Mariette, Peter Merkel, Eduardo F. Mysler, Peter Nash, Michael T. Nurmohamed, Karel Pavelka, Gyula Poor, Andrea Rubbert-Roth, Hendrik Schulze-Koops, Anja Strangfeld, Yoshiya Tanaka, Josef S. Smolen
Summary: This paper is an updated consensus document on the medical use of IL-6 pathway inhibition in the treatment of inflammatory diseases. The document provides comprehensive consensus statements based on systematic literature research and expert opinion, covering various aspects of IL-6 pathway inhibitors, including dosing, indications, and clinical considerations.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
E. B. Rasmussen, L. S. Thiele, K. Stengaard-Pedersen, M. L. Hetland, K. Horslev-Petersen, P. Junker, M. Ostergaard, A. S. Hansen, M. Hvid, B. Deleuran, S. R. Greisen
Summary: ACPAs IgA and IgG have weak associations with disease activity in early RA, but are not superior in predicting long-term radiographic progression.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
M. Pfeiffer-Jensen, D. Liao, U. Tarp, B. Deleuran, K. Stengaard-Pedersen, J. Venborg, B. Brock, C. Brock
Summary: This study examines the use of therapeutic drug monitoring (TDM) to personalize the dosing of TNF-alpha inhibitors, finding that it reduces drug prescription and prolongs treatment intervals. Additionally, TDM allows for the identification of patients who would benefit from a drug switch, minimizing treatment failure and unnecessary adverse events.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Immunology
Kathrine Pedersen, Morten Aagaard Nielsen, Kristian Juul-Madsen, Malene Hvid, Bent Deleuran, Stinne Ravn Greisen
Summary: This study focuses on impaired PD-1 signalling and upregulation of Galectin-3 (Gal-3) in rheumatoid arthritis (RA). The results show that Gal-3 binds PD-1 and PD-L1, inhibiting PD-1 signalling when PD-L1 is present. High expression of PD-1 and Gal-3 is observed on mononuclear cells, especially from synovial fluid (SF). Gal-3 also affects osteoclast formation directly and through PD-1:PD-L1 inhibition. The inhibitory role of Gal-3 on the PD-1 signalling axis suggests that targeting Gal-3 could have therapeutic potential in RA.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2023)
Correction
Rheumatology
Lykke M. Ornbjerg, Louise Linde, Stylianos Georgiadis, Simon H. Rasmussen, Ulf Lindstrom, Johan Askling, Brigitte Michelsen, Daniela Di Giuseppe, Johan K. Wallman, Karel Pavelka, Jakub Zavada, Michael J. Nissen, Gareth T. Jones, Heikki Relas, Laura Pirila, Matija Tomsic, Ziga Rotar, Arni Jon Geirsson, Bjorn Gudbjornsson, Eirik K. Kristianslund, Irene van der Horst-Bruinsma, Anne Gitte Loft, Karin Laas, Florenzo Iannone, Addolorata Corrado, Adrian Ciurea, Maria J. Santos, Helena Santos, Catalin Codreanu, Nurullah Akkoc, Ozgul S. Gunduz, Bente Glintborg, Mikkel Ostergaard, Merete Lund Hetland
SEMINARS IN ARTHRITIS AND RHEUMATISM
(2023)
Article
Cell Biology
Morten A. A. Nielsen, Ditte Koster, Akul Y. Y. Mehta, Kristian Stengaard-Pedersen, Pierre Busson, Peter Junker, Kim Horslev-Petersen, Merete Lund Hetland, Mikkel ostergaard, Malene Hvid, Hakon Leffler, Tue W. W. Kragstrup, Richard D. D. Cummings, Bent Deleuran
Summary: This study evaluated the clinical and pathogenic aspects of Gal-9 in rheumatoid arthritis (RA) and found that it plays a role in modulating synovial FLS activities and maintaining subclinical disease activity.
Review
Public, Environmental & Occupational Health
Kristina Laugesen, Jonas Mengel-From, Kaare Christensen, Jorn Olsen, David M. Hougaard, Lasse Boding, Anja Olsen, Christian Erikstrup, Merete Lund Hetland, Estrid Hogdall, Alisa Kjaergaard, Erik Sorensen, Anja Brugmann, Eva Rabing Brix Petersen, Ivan Brandslund, Borge Nordestgaard, Gorm B. Jensen, Nils Skajaa, Frederikke Schonfeldt Troelsen, Cecilia Hvitfeldt Fuglsang, Lise Skovgaard Svingel, Henrik T. Sorensen
Summary: Denmark has a rich source of biobanks and a comprehensive healthcare system, which allows for the integration of biological specimens with clinical and demographic data for biobank research. This can contribute to a better understanding of disease etiology and personalized medicine.
CLINICAL EPIDEMIOLOGY
(2023)
Article
Medicine, Research & Experimental
Marie Louise Naestholt Dahl, Jakob Hauge Mikkelsen, Malene Hvid, Trine-Line Korsholm, Kirstine Overgaard Nielsen, Christian Brix Folsted Andersen, Stinne Greisen, Bent Deleuran
Summary: We established an indirect ELISA method to detect autoantibodies against full-length TRIM21 protein and its four domains, and validated the efficacy using plasma from anti-SSA positive patients and healthy controls. Our results showed significantly higher levels of autoantibodies against full-length TRIM21, PRY/SPRY, Coiled-Coil, and RING domains in patients compared to healthy controls. There was no significant difference in autoantibody levels against the B-box domain. Our protocols allow for further study of different autoantibodies in anti-SSA positive patients, enabling stratification of patients based on autoantibody profile and specific phenotypes or endotypes.
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION
(2023)
Article
Cell Biology
Aida S. S. Hansen, Lea S. S. Jensen, Kristine R. R. Gammelgaard, Kristoffer G. G. Ryttersgaard, Christian Krapp, Jesper Just, Kasper L. L. Jonsson, Pia B. B. Jensen, Thomas Boesen, Mogens Johansen, Anders Etzerodt, Bent W. W. Deleuran, Martin R. R. Jakobsen
Summary: This article introduces the highly immunosuppressive tumor microenvironment, and explores a novel method to improve immunotherapy effectiveness by activating the STING signaling pathway. The researchers found that extracellular vesicles derived from activated CD4(+) T cells can sensitize macrophages and activate the STING pathway, effectively disrupting the immune suppressive environment in the tumor and priming for a robust immune response towards STING activation.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Rheumatology
Helga Westerlind, Bente Glintborg, Hilde Berner Hammer, Saedis Saevarsdottir, Niels Steen Krogh, Merete Lund Hetland, Ellen-Margrethe Hauge, Isabel Martinez Tejada, Joseph Sexton, Johan Askling
Summary: This study aims to describe how data harmonization can be achieved in rheumatoid arthritis (RA) and found that the proportion of patients reaching remission in RA treatment is low.
Article
Rheumatology
Janni Maria Pedersen, Aida Solhoj Hansen, Caecilie Skejo, Kristian Juul-Madsen, Peter Junker, Kim Horslev-Petersen, Merete Lund Hetland, Kristian Stengaard-Pedersen, Mikkel ostergaard, Bjarne Kuno Moller, Lene Dreyer, Ellen-Margrethe Hauge, Malene Hvid, Stinne Greisen, Bent Deleuran
Summary: This study investigated the role of lymphocyte activation gene-3 (LAG-3) as a serological marker and mediator in the pathogenesis of rheumatoid arthritis (RA). The results showed increased levels of LAG-3 in both early and chronic RA patients, particularly in the inflamed joint. LAG-3 plays a biological role in reducing inflammatory cytokine production in chronic RA, and this function is not affected by Gal-3 interference. Our findings suggest that LAG-3 is a multifaceted regulator of inflammation in early and chronic RA.
ARTHRITIS RESEARCH & THERAPY
(2023)
Article
Rheumatology
Tanja Thomsen, Mette Aadahl, Merete Lund Hetland, Bente Appel Esbensen
Summary: A higher proportion of rheumatoid arthritis patients are physically inactive. Lack of consistent physical activity guidance from health professionals may be a barrier. This study explores patients' perspectives on current and future guidance and emphasizes the importance of integrated physical activity focus in rheumatology clinics, with adequate training for health professionals.
RHEUMATOLOGY INTERNATIONAL
(2023)