Article
Immunology
Cristina Cocco, Elias Manca, Giulia Corda, Maria Maddalena Angioni, Barbara Noli, Mattia Congia, Francesco Loy, Michela Isola, Elisabetta Chessa, Alberto Floris, Lorena Lorefice, Luca Saba, Alessandro Mathieu, Gian Luca Ferri, Alberto Cauli, Matteo Piga
Summary: Brain-reactive autoantibodies are found in patients with SLE and NPSLE, with higher frequency and titers observed in NPSLE patients. The target antigens of these autoantibodies are still undetermined, but they likely include β2GPI.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Simone Caielli, Zurong Wan, Virginia Pascual
Summary: Autoreactive B cells and interferons play important roles in the development of systemic lupus erythematosus (SLE). Recent studies on genetics and immune monitoring of SLE patients have provided new insights into the underlying mechanisms, including novel gene mutations affecting B cell activation and clearance of interferogenic nucleic acids. Mitochondria have been identified as inducers or amplifiers of SLE through various mechanisms, leading to the release of interferogenic nucleic acids and activation of immune cells. Specific autoantibodies associated with monogenic lupus or triggering interferogenic amplification loops have been discovered. Additionally, atypical B cells and novel T helper cell subsets have been proposed to contribute to the generation of SLE autoantibodies. These findings offer opportunities for improved monitoring and personalized therapy for SLE patients.
ANNUAL REVIEW OF IMMUNOLOGY
(2023)
Editorial Material
Cell Biology
Simon Fillatreau
Summary: The study reveals that autoantibodies in systemic lupus erythematosus (SLE) can have a protective role by neutralizing type I interferons (IFNs) and restraining the activation of pathogenic B cells.
CELL REPORTS MEDICINE
(2023)
Article
Cell Biology
Imene Melki, Isabelle Allaeys, Nicolas Tessandier, Tania Levesque, Nathalie Cloutier, Audree Laroche, Nathalie Vernoux, Yann Becker, Hadrien Benk-Fortin, Anne Zufferey, Emmanuelle Rollet-Labelle, Marc Pouliot, Guy Poirier, Natacha Patey, Clemence Belleannee, Denis Soulet, Steven E. McKenzie, Alain Brisson, Marie-Eve Tremblay, Christian Lood, Paul R. Fortin, Eric Boilard
Summary: The study reveals that platelets release mitochondrial DNA in patients with SLE, and this process is associated with platelet degranulation and requires stimulation of platelet Fc-γ-RIIA.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Andreas Mackensen, Fabian Mueller, Dimitrios Mougiakakos, Sebastian Boeltz, Artur Wilhelm, Michael Aigner, Simon Voelkl, David Simon, Arnd Kleyer, Luis Munoz, Sascha Kretschmann, Soraya Kharboutli, Regina Gary, Hannah Reimann, Wolf Roesler, Stefan Uderhardt, Holger Bang, Martin Herrmann, Arif Buelent Ekici, Christian Buettner, Katharina Maria Habenicht, Thomas H. Winkler, Gerhard Kroenke, Georg Schett
Summary: A study of five patients with refractory systemic lupus erythematosus treated with anti-CD19 CAR T cell therapy showed remission of SLE disease in all patients after 3 months, and long-term drug-free remission was maintained during follow-up.
Review
Rheumatology
Mary K. Crow
Summary: Research has identified type I interferon (IFN-I) and autoantibodies targeting nucleic acids and nucleic acid-binding proteins as fundamental contributors to the pathogenesis of systemic lupus erythematosus (SLE). This review summarizes recent genetic analyses of SLE patients and current studies on innate and adaptive immune function, which contribute to sustained IFN-I pathway activation, immune activation, autoantibody production, inflammatory mediator generation, and tissue damage. The goal of these studies is to understand disease mechanisms, identify therapeutic targets, and develop better treatments for patients.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
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
Rheumatology
May Yee Choi, Irene Chen, Ann Elaine Clarke, Marvin J. Fritzler, Katherine A. Buhler, Murray Urowitz, John Hanly, Yvan St-Pierre, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Daniel J. Wallace, David Alan 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, Kenneth Kalunian, Soren Jacobsen, Christine Peschken, Diane L. Kamen, Anca Askanase, Jill P. Buyon, David Sontag, Karen H. Costenbader
Summary: A novel longitudinal clustering technique was used to analyze comprehensive autoantibody data from a large, well-characterised, multinational inception SLE cohort, in order to determine predictive profiles of clinical outcomes.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Immunology
Jiaxuan Chen, Shuzhen Liao, Huimin Zhou, Lawei Yang, Fengbiao Guo, Shuxian Chen, Aifen Li, Quanren Pan, Chen Yang, Hua-feng Liu, Qingjun Pan
Summary: Animal models play a crucial role in understanding human diseases, but they cannot fully simulate the occurrence and progression of diseases due to genetic and disease-specific differences. Humanized immune system mice, developed from immunodeficient mice, provide a partial reconstruction of the human immune system and mimic the in vivo microenvironment. However, there are challenges in developing humanized mice models for systemic lupus erythematosus (SLE), including improving immune response reconstruction efficiency, extending observation period, and improving model development and utilization.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Lisa Abernathy-Close, Stephanie Lazar, Jasmine Stannard, Lam C. Tsoi, Sean Eddy, Syed M. Rizvi, Christine M. Yee, Emily M. Myers, Rajaie Namas, Lori Lowe, Tamra J. Reed, Fei Wen, Johann E. Gudjonsson, J. Michelle Kahlenberg, Celine C. Berthier
Summary: Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease that commonly occurs in patients with systemic lupus erythematosus (SLE) and can also develop in the absence of systemic disease. Research has shown that skin-associated B cell responses distinguish CLE subtypes, with B cell function possibly being an important link between cutaneous lupus and systemic disease activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Christina Adamichou, Irini Genitsaridi, Dionysis Nikolopoulos, Myrto Nikoloudaki, Argyro Repa, Alessandra Bortoluzzi, Antonis Fanouriakis, Prodromos Sidiropoulos, Dimitrios T. Boumpas, George K. Bertsias
Summary: A machine learning algorithm was developed to assist in the diagnosis of SLE by analyzing patient data sets, leading to improved diagnostic and treatment outcomes.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Allergy
Xin Huang, Qing Zhang, Huilin Zhang, Qianjin Lu
Summary: This article provides new insights into the diagnosis of SLE by summarizing recent advances in epidemiology, etiology, classification criteria, clinical manifestations, and the study of autoantibodies. Based on these recent advances, earlier diagnosis and more personalized medicine can be achieved.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2022)
Review
Immunology
Gabriela Guzman-Martinez, Concepcion Maranon
Summary: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD), which is becoming one of the most relevant complications and a significant factor causing morbidity and mortality in SLE. Immune constituents, including specific circulating cell populations, autoantibodies, and inflammatory mediators, play a role in the pathogenesis of atherosclerosis and endothelial damage in SLE patients. This review summarizes the presentation of CVD in SLE, the role of autoimmune responses in inducing atherogenesis, endothelial impairment, and cardiac disease, and discusses the utility of immune mediators as early CVD biomarkers and targets for clinical intervention in SLE patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
M. Constanza Baroni Pietto, Paola R. Lev, Ana C. Glembotsky, Cecilia P. Marin Oyarzun, Graciela Gomez, Victoria Collado, Cecilia Pisoni, Ramiro A. Gomez, Matias Grodzielski, Jacqueline Gonzalez, Karina Marino, Paula G. Heller, Nora P. Goette, Rosana F. Marta
Summary: The study found that systemic lupus erythematosus (SLE) patients with thrombocytopenia have abnormalities in platelet clearance and production, mainly due to apoptosis and desialylation leading to low platelet count. These abnormalities are more frequently observed in patients with thrombocytopenia and active disease.
Review
Rheumatology
Eduardo Gomez-Banuelos, Andrea Fava, Felipe Andrade
Summary: Autoantibodies play a crucial role in systemic lupus erythematosus (SLE) as they cause tissue damage. They provide information about disease susceptibility, clinical course, outcomes, and the cause of SLE. However, identifying pathogenic autoantibodies in SLE is still challenging. This review summarizes recent advances in the field of autoantibodies in SLE.
CURRENT OPINION IN RHEUMATOLOGY
(2023)
Article
Immunology
Wei Luo, William Hawse, Laura Conter, Nikita Trivedi, Florian Weisel, Daniel Wikenheiser, Richard T. Cattley, Mark J. Shlomchik
Article
Immunology
Kerstin Nundel, Purvi Mande, Stephanie L. Moses, Patricia Busto, Jaime L. Cullen, Madelyn R. Schmidt, Mark J. Shlomchik, Robert T. Woodland, Ann Marshak-Rothstein
JOURNAL OF IMMUNOLOGY
(2019)
Article
Immunology
Nikita Trivedi, Florian Weisel, Shuchi Smita, Stephen Joachim, Muhamuda Kader, Aditya Radhakrishnan, Chris Clouser, Aaron M. Rosenfeld, Maria Chikina, Francois Vigneault, Uri Hershberg, Nahed Ismail, Mark Jay Shlomchik
Article
Immunology
Florian J. Weisel, Steven J. Mullett, Rebecca A. Elsner, Ashley V. Menk, Nikita Trivedi, Wei Luo, Daniel Wikenheiser, William F. Hawse, Maria Chikina, Shuchi Smita, Laura J. Conter, Stephen M. Joachim, Stacy G. Wendell, Michael J. Jurczak, Thomas H. Winkler, Greg M. Delgoffe, Mark J. Shlomchik
Article
Medicine, Research & Experimental
Jeremy S. Tilstra, Shinu John, Rachael A. Gordon, Claire Leibler, Michael Kashgarian, Sheldon Bastacky, Kevin M. Nickerson, Mark J. Shlomchik
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Multidisciplinary Sciences
Rachael A. Gordon, Jeremy S. Tilstra, Anthony Marinov, Kevin M. Nickerson, Sheldon Bastacky, Mark J. Shlomchik
Article
Hematology
Nadine M. Weisel, Florian J. Weisel, Donna L. Farber, Lisa A. Borghesi, Yufeng Shen, Wenji Ma, Eline T. Luning Prak, Mark J. Shlomchik
Article
Rheumatology
Anthony D. Marinov, Haowei Wang, Sheldon I. Bastacky, Erwin van Puijenbroek, Thomas Schindler, Dario Speziale, Mario Perro, Christian Klein, Kevin M. Nickerson, Mark J. Shlomchik
Summary: The study found that obinutuzumab (GA101) was more effective than rituximab (RTX) in depleting B cells in diseased MRL/lpr mice, with better treatment outcomes in early disease including reduced glomerulonephritis, lower anti-RNA autoantibody titers, and fewer activated CD4+ T cells. GA101 also prolonged survival in an advanced disease model.
ARTHRITIS & RHEUMATOLOGY
(2021)
Article
Immunology
Nadine M. Weisel, Stephen M. Joachim, Shuchi Smita, Derrick Callahan, Rebecca A. Elsner, Laura J. Conter, Maria Chikina, Donna L. Farber, Florian J. Weisel, Mark J. Shlomchik
Summary: The study conducted a large-scale screening of memory B cells in humans and mice, identifying numerous surface proteins that are differentially expressed between MBCs and NBCs, providing insight into their functional differences.
Article
Medicine, Research & Experimental
Shuchi Smita, Maria Chikina, Mark J. Shlomchik, Jeremy S. Tilstra
Summary: In murine lupus nephritis, kidney-infiltrating T cells resemble dysfunctional T cells that infiltrate tumors. The kidney microenvironment suppresses T cells by progressively inducing exhausted states. These findings have implications for both autoimmunity and tumor immunology.
Article
Immunology
Wei Luo, Laura Conter, Rebecca A. Elsner, Shuchi Smita, Florian Weisel, Derrick Callahan, Shuxian Wu, Maria Chikina, Mark Shlomchik
Summary: IL-21R plus CD40 signals have different effects on germinal center B cells compared with BCR plus CD40 signals, leading to the differentiation of a subset of cells into plasma cells, representing a second positive selection pathway.
SCIENCE IMMUNOLOGY
(2023)
Article
Immunology
Jeremy S. Tilstra, Minjung Kim, Rachael A. Gordon, Claire Leibler, Haylee A. Cosgrove, Sheldon Bastacky, Kevin M. Nickerson, Mark J. Shlomchik
Summary: Studies have shown that MyD88 in B cells plays a crucial role in the onset and progression of lupus in mice, and its deficiency can improve disease symptoms and reduce autoantibody production. Therefore, targeting MyD88 or its upstream activators may be an effective option for treating lupus.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Haylee A. Cosgrove, Sebastien Gingras, Minjung Kim, Sheldon Bastacky, Jeremy S. Tilstra, Mark J. Shlomchik
Summary: The regulatory role of Toll-like receptor 7 (TLR7) in the pathogenesis of lupus and its potential therapeutic strategy have been studied. The study found that TLR7 deficiency in B cells greatly improved the disease progression in TLR9-deficient mice with accelerated systemic lupus erythematosus, suggesting the importance of B cell-directed TLR7 regulation in lupus.
Meeting Abstract
Rheumatology
Jeremy Tilstra, Minjung Kim, Claire Leibler, Mark Shlomchik
ARTHRITIS & RHEUMATOLOGY
(2019)
Article
Medicine, Research & Experimental
Travis B. Lear, Alison C. McKelvey, John W. Evankovich, Shristi Rajbhandari, Tiffany A. Coon, Sarah R. Dunn, James D. Londino, Bryan J. McVerry, Yingze Zhang, Eleanor Valenzi, Christine L. Burton, Rachael Gordon, Sebastien Gingras, Karina C. Lockwood, Michael J. Jurczak, Robert Lafyatis, Mark J. Shlomchik, Yuan Liu, Bill B. Chen