Review
Biochemistry & Molecular Biology
Madhu Ramaswamy, Raj Tummala, Katie Streicher, Andre Nogueira da Costa, Philip Z. Brohawn
Summary: Systemic lupus erythematosus (SLE) presents a challenging treatment landscape due to its multifaceted etiology and complex immunopathogenesis. While targeting the B-cell pathway has limitations, recent approval of anifrolumab, a type I interferon-blocking antibody, highlights the therapeutic potential of targeting the dysregulated interferon pathway in SLE patients. Further research into the pleiotropic biology of interferons and their intersection with SLE disease pathology will be crucial for the development of effective targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Multidisciplinary Sciences
Ioana Saulescu, Ruxandra Ionescu, Daniela Opris-Belinski
Summary: Although perceived as an adaptative immune disorder, last years' focus on Systemic Lupus Erythematosus (SLE) pathogeny emphasized the important role of innate immunity. Failure of the immune mechanisms to preserve the balance between autoinflammation and autoimmunity initiates and propagates SLE, with interferon being a key cytokine in this process.
Article
Biochemistry & Molecular Biology
Tom Aschman, Sandra Schaffer, Stylianos Iason Biniaris Georgallis, Antigoni Triantafyllopoulou, Peter Staeheli, Reinhard E. Voll
Summary: The role of type III interferons in systemic lupus erythematosus has been increasingly studied, with evidence suggesting their involvement in regulating immune responses and promoting inflammation. In a lupus disease model, mice lacking type III interferon receptors showed improved survival rates, reduced autoantibody production, and decreased inflammatory cell infiltration in the kidneys, indicating a potential protective effect of inhibiting type III interferon signaling in autoimmunity development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, General & Internal
Kennedy C. Ukadike, Tomas Mustelin
Summary: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a multifactorial etiology involving genetic, immunologic, hormonal, and environmental factors. The hypothesis proposes that L1 retrotransposons play a key role in SLE pathogenesis by activating type I interferon production and inducing immune responses similar to chronic viral infections. Understanding the role of L1 retroelements in SLE may lead to new diagnostic, prognostic, and therapeutic strategies for the disease.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cell Biology
Jodi L. Karnell, Yanping Wu, Nanette Mittereder, Michael A. Smith, Michele Gunsior, Li Yan, Kerry A. Casey, Jill Henault, Jeffrey M. Riggs, Simone M. Nicholson, Miguel A. Sanjuan, Katherine A. Vousden, Victoria P. Werth, Jorn Drappa, Gabor G. Illei, William A. Rees, John N. Ratchford
Summary: Plasmacytoid dendritic cells (pDCs) are specialized in producing IFN and regulating immune responses, with persistent activation in autoimmune diseases. VIB7734, a monoclonal antibody, effectively depletes pDCs, reduces IFN activity, and improves clinical disease activity in animal models and patients. Biomarker analysis suggests that VIB7734 may be more effective in individuals with high baseline IFN activity, supporting further development in IFN-associated diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Review
Immunology
Paul Curtiss, Amanda M. Walker, Benjamin F. Chong
Summary: This study reviewed patient cohorts and populations to investigate the progression of cutaneous lupus to systemic lupus. The study found variations in the progression rates between adult and pediatric groups, which were attributed to differences in patient populations, study design, diagnostic criteria, and follow-up time. Risk factors associated with the development of systemic lupus included positive anti-nuclear antibodies, hematologic abnormalities, and a higher number of lupus classification criteria at baseline.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dario Roccatello, Roberta Fenoglio, Ilaria Caniggia, Joelle Kamgaing, Carla Naretto, Irene Cecchi, Elena Rubini, Daniela Rossi, Emanuele De Simone, Giulio Del Vecchio, Martina Cozzi, Savino Sciascia
Summary: This study presents a case series of six patients with refractory lupus nephritis who were treated with an off-label anti-CD38 monoclonal antibody. Five patients achieved complete or partial renal responses after 12 months of follow-up. These findings suggest that daratumumab monotherapy shows promise as a potential treatment for refractory lupus nephritis.
Article
Multidisciplinary Sciences
Sabina Sangaletti, Laura Botti, Alessandro Gulino, Daniele Lecis, Barbara Bassani, Paola Portararo, Matteo Milani, Valeria Cancila, Loris De Cecco, Matteo Dugo, Claudio Tripodo, Mario P. Colombo
Summary: SPARC plays a crucial role in autoimmune diseases, and its down-regulation may be a key event in the pathogenesis of SLE and rheumatoid arthritis.
Article
Immunology
Helena Enocsson, Birgitta Gullstrand, Maija-Leena Eloranta, Jonas Wettero, Dag Leonard, Lars Ronnblom, Anders A. Bengtsson, Christopher Sjowall
Summary: In patients with systemic lupus erythematosus (SLE) during a quiescent phase, IL-6 levels, CRP genotype (rs1205), and type I interferon (IFN) gene signature have an impact on basal CRP levels, with IL-6 positively associated and IGS positivity and CRP genotype (rs1205) AA/GA negatively associated with CRP levels.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Norzawani Buang, Lunnathaya Tapeng, Victor Gray, Alessandro Sardini, Chad Whilding, Liz Lightstone, Thomas D. Cairns, Matthew C. Pickering, Jacques Behmoaras, Guang Sheng Ling, Marina Botto
Summary: This study reveals that high expression of type I interferon in SLE patients affects mitochondrial function and cell metabolism in CD8(+) T cells, leading to cell death. Furthermore, these abnormalities can be corrected by NAD+ supplementation.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Helena Idborg, Vilija Oke
Summary: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by activation and dysregulation of the immune system. Disturbances in immune pathways and genetic susceptibility are key factors in the development of SLE. Dysregulation of cytokines, particularly interferons, has been extensively studied as potential biomarkers and treatment targets in SLE.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Qian Chen, Jie Wang, Mengmeng Xiang, Yilun Wang, Zhixiong Zhang, Jun Liang, Jinhua Xu
Summary: This review summarizes the potential links between ferroptosis and systemic lupus erythematosus (SLE), elucidates the role of ferroptosis in SLE pathogenesis, and proposes a new therapeutic strategy for SLE.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Patrick Coit, Xiavan Roopnarinesingh, Lourdes Ortiz-Fernandez, Kathleen McKinnon-Maksimowicz, Emily E. Lewis, Joan T. Merrill, W. Joseph McCune, Jonathan D. Wren, Amr H. Sawalha
Summary: This study analyzed the genome-wide DNA methylation of lupus patients and found that in addition to the hypomethylation of interferon-regulated genes, the miR-17-92 cluster also showed hypomethylation in patients with lupus, which is associated with T cell activation. The expression of miR-19b1 and miR-18a was significantly correlated with lupus disease activity.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
May Yee Choi, Ann Elaine Clarke, Murray Urowitz, John Hanly, Yvan St-Pierre, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Daniel J. Wallace, David Isenberg, Anisur Rahman, Joan T. Merrill, Paul R. Fortin, Dafna D. Gladman, Ian N. Bruce, Michelle Petri, Ellen M. Ginzler, Mary Anne Dooley, Rosalind Ramsey-Goldman, Susan Manzi, Andreas Jonsen, Graciela S. Alarcon, Ronald F. van Vollenhoven, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Ken Kalunian, Soren Jacobsen, Christine Peschken, Diane L. Kamen, Anca Askanase, Jill P. Buyon, Karen H. Costenbader, Marvin J. Fritzler
Summary: In a longitudinal analysis of a large international incident SLE cohort, three ANA assays demonstrated high positivity rates and commutability. However, over a 5-year follow-up, there was a modest variation in ANA assay performance.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Cell Biology
Guoping Shi, Dan Li, Dongya Zhang, Yujun Xu, Yuchen Pan, Li Lu, Jingman Li, Xiaoyu Xia, Huan Dou, Yayi Hou
Summary: This study found that the percentage of M-MDSCs increased in pristane-induced lupus mice, and the differentiation of M-MDSCs was promoted by Toll-like receptor 7 signal activation and high interferon-alpha levels. Additionally, the AMPK agonist metformin and mTOR inhibitors were found to inhibit M-MDSC percentages in lupus mice as well as in vitro differentiation into MDSCs induced by TLR7 and IFN-alpha.
CELL DEATH DISCOVERY
(2021)