Review
Immunology
Michele Fresneda Alarcon, Zoe McLaren, Helen Louise Wright
Summary: Dysregulated neutrophil activation plays a significant role in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, contributing to inflammation and autoantibody production in both autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jessica M. Jones, Frances Smith, Emily Littlejohn, Trine N. Jorgensen
Summary: This study aims to investigate the relative role of sex and sex hormones on the frequency and function of pDCs, MDSCs, and LDGs in SLE patients. The results showed that regardless of sex and sex hormone levels, male and female SLE patients exhibited similar alterations in the frequencies of pDCs, MDSCs, and LDGs, expression of TLR7 and TLR9, and production of TLR9-driven cytokines.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Katherine R. Martin, Jessica A. Day, Jacinta A. Hansen, Damian B. D'Silva, Huon L. Wong, Alexandra Garnham, Jarrod J. Sandow, Brunda Nijagal, Nicholas Wilson, Ian P. Wicks
Summary: Low-density neutrophils (LDN), a subset of neutrophils, are found in the blood of patients with autoimmune diseases such as systemic lupus erythematosus (SLE). This study identified CD98 as a marker for LDN in SLE patients. CD98 is responsible for the increased bioenergetic capacity of LDN, as it mediates the uptake of essential amino acids by mitochondria. CD98(+) LDN produce more proinflammatory cytokines and chemokines and are resistant to apoptosis. CD98 represents a potential therapeutic target to limit the pathogenic capacity of LDN.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Immunology
Swayanka Biswas, Katja Bieber, Rudolf Armin Manz
Summary: IL-10 is a cytokine that has pleiotropic effects on immune cells, including both suppressive and activating functions. It plays a dual role in Systemic lupus Erythematosus (SLE), inhibiting pro-inflammatory effector functions while also promoting extrafollicular antibody response. IL-10 is produced by B cells, myeloid cells, and certain T cell subsets, and it drives B cell responses, proliferation, class switching, and plasma cell formation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Hao Cheng, Xiao-ying Zhang, Hui-dan Yang, Zhen Yu, Cheng-lan Yan, Chong Gao, Hong-yan Wen
Summary: This study showed that Belimumab in combination with low-dose intravenous CYC significantly reduced disease activity scores and maintained the B/T cell balance for SLE patients at 24 weeks. The Belimumab treatment group had lower adverse events and higher efficacy compared to conventional treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Ji-Won Kim, Wook-Young Baek, Ju-Yang Jung, Hyoun-Ah Kim, Cheong In Yang, Seung-Ju Kim, Chang-Hee Suh
Summary: This study found that seasonal vitamin D levels are correlated with clinical manifestations and disease activity in lupus patients. Adequate vitamin D levels are important for achieving a low disease activity state in both winter and summer.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Rheumatology
Fan Yang, Jin Lin, Weiqian Chen
Summary: Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized by multiple autoantibodies and immune-mediated tissue damage. While a new drug, belimumab, shows promise in improving SLE conditions, the discovery of novel therapeutic targets is urgently needed. Protein post-translational modifications (PTMs) may play key roles in regulating T-cell function and signaling pathways in SLE pathogenesis, presenting potential new targets for therapy.
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
Rheumatology
Kathleen R. Bashant, Angel M. Aponte, Davide Randazzo, Paniz Rezvan Sangsari, Alexander J. T. Wood, Jack A. Bibby, Erin E. West, Arlette Vassallo, Zerai G. Manna, Martin P. Playford, Natasha Jordan, Sarfaraz Hasni, Marjan Gucek, Claudia Kemper, Andrew Conway Morris, Nicole Y. Morgan, Nicole Toepfner, Jochen Guck, Nehal N. Mehta, Edwin R. Chilvers, Charlotte Summers, Mariana J. Kaplan
Summary: The study identified proteomic differences and rougher cell surfaces in SLE LDGs compared to SLE NDNs, suggesting potential increased retention in microvasculature networks.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Immunology
Hao Li, Afroditi Boulougoura, Yushiro Endo, George C. Tsokos
Summary: T cell abnormalities are closely associated with the development of SLE, including numerical and functional disturbances in CD4+ and CD8+ T cells, which lead to immune dysregulation and tissue infiltration. These abnormalities are mainly due to signaling defects, metabolic alterations, and epigenetic changes. Novel strategies to correct T cell abnormalities show promise for SLE treatment.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Rheumatology
Ming Zhao, Delong Feng, Longyuan Hu, Lin Liu, Jiali Wu, Zhi Hu, Haojun Long, Qiqi Kuang, Lianlian Ouyang, Qianjin Lu
Summary: This study aimed to elucidate the three-dimensional genome structure and its impact on gene expression networks in systemic lupus erythematosus (SLE). Through analysis of CD4(+) T cells from SLE patients and healthy controls, it was found that SLE patients had distinct genome structures compared to healthy controls, which were closely associated with disease activity. Additionally, loops within chromosomes associated with disease activity and differentially expressed genes were identified, along with key histone modifications close to these loops. The study provides a foundation for further investigation into the relationship between chromosome structure and gene expression control in SLE.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Oncology
Kaichi Kaneko, Hao Chen, Matthew Kaufman, Isaak Sverdlov, Emily M. Stein, Kyung-Hyun Park-Min
Summary: Osteonecrosis is a complex and devastating complication of systemic lupus erythematosus, with variable prevalence in SLE patients. The use of high-dose glucocorticoid therapy is strongly associated with the development of osteonecrosis in SLE patients, although the exact pathophysiology and risk factors for osteonecrosis in this population are not fully understood.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Valeria Rella, Cinzia Rotondo, Alberto Altomare, Francesco Paolo Cantatore, Addolorata Corrado
Summary: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations. Dysregulation of the immune system due to genetic, hormonal, and environmental factors can lead to various complications, including bone involvement such as osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Shunxiang Li, Huihua Ding, Ziheng Qi, Jing Yang, Jingyi Huang, Lin Huang, Mengji Zhang, Yuanjia Tang, Nan Shen, Kun Qian, Qiang Guo, Jingjing Wan
Summary: Serum metabolic fingerprints can be used for disease diagnosis and biomarker discovery. By analyzing the serum metabolic fingerprints of systemic lupus erythematosus (SLE) patients and healthy controls, early diagnosis and precision medicine for SLE can be achieved. This study identified the unique metabolic pattern of SLE patients and screened out a panel of metabolic biomarkers.
Article
Immunology
Tao Cheng, Shuai Ding, Shanshan Liu, Xiaojing Li, Xiaojun Tang, Lingyun Sun
Summary: The study showed that RvD1 levels were significantly lower in active SLE patients compared to inactive individuals and controls, which correlated negatively with SLE disease activity. Treatment with RvD1 improved disease phenotype and inflammation in MRL/lpr mice, as well as rebalanced Treg/Th17 differentiation. Moreover, RvD1 was found to increase Treg and decrease Th17 differentiation in vitro, with miR-30e-5p identified as a key downstream microRNA regulating this process.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Heeseog Kang, Smita Jha, Aleksandra Ivovic, Nadja Fratzl-Zelman, Zuoming Deng, Apratim Mitra, Wayne A. Cabral, Eric P. Hanson, Eileen Lange, Edward W. Cowen, James Katz, Paul Roschger, Klaus Klaushofer, Ryan K. Dale, Richard M. Siegel, Timothy Bhattacharyya, Joan C. Marini
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Multidisciplinary Sciences
Divya Sagar, Ranjitha Gaddipati, Emily L. Ongstad, Nicholas Bhagroo, Ling-Ling An, Jingya Wang, Mehdi Belkhodja, Saifur Rahman, Zerai Manna, Michael A. Davis, Sarfaraz Hasni, Richard Siegel, Miguel Sanjuan, Joseph Grimsby, Roland Kolbeck, Sotirios Karathanasis, Gary P. Sims, Ruchi Gupta
Article
Multidisciplinary Sciences
Michael A. Smith, Chia-Chien Chiang, Kamelia Zerrouki, Saifur Rahman, Wendy White, Katie Streicher, William A. Rees, Adam Schiffenbauer, Lisa G. Rider, Frederick W. Miller, Zerai Manna, Sarfaraz Hasni, Mariana J. Kaplan, Richard Siegel, Dominic Sinibaldi, Miguel A. Sanjuan, Kerry A. Casey
SCIENTIFIC REPORTS
(2020)
Letter
Dermatology
Smita Jha, Aleksandra Ivovic, Heeseog Kang, Francoise Meylan, Eric P. Hanson, Casey Rimland, Eileen Lange, James Katz, Alison McBride, Andrew C. Warner, Elijah F. Edmondson, Edward W. Cowen, Joan C. Marini, Richard M. Siegel, Timothy Bhattacharyya
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Chenzhi Jing, Tomas Castro-Dopico, Nathan Richoz, Zewen K. Tuong, John R. Ferdinand, Laurence S. C. Lok, Kevin W. Loudon, Gemma D. Banham, Rebeccah J. Mathews, Zaeem Cader, Susan Fitzpatrick, Kathleen R. Bashant, Mariana J. Kaplan, Arthur Kaser, Randall S. Johnson, Michael P. Murphy, Richard M. Siegel, Menna R. Clatworthy
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Medicine, Research & Experimental
Ainhoa Perez-Diez, Chun-Shu Wong, Xiangdong Liu, Harry Mystakelis, Jian Song, Yong Lu, Virginia Sheikh, Jeffrey S. Bourgeois, Andrea Lisco, Elizabeth Laidlaw, Cornelia Cudrici, Chengsong Zhu, Quan-Zhen Li, Alexandra F. Freeman, Peter R. Williamson, Megan Anderson, Gregg Roby, John S. Tsang, Richard Siegel, Irini Sereti
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Rheumatology
Kerry A. Casey, Michael A. Smith, Dominic Sinibaldi, Nickie L. Seto, Martin P. Playford, Xinghao Wang, Philip M. Carlucci, Liangwei Wang, Gabor Illei, Binbing Yu, Shiliang Wang, Alan T. Remaley, Nehal N. Mehta, Mariana J. Kaplan, Wendy White
Summary: The study suggests that blocking the type I IFN receptor with anifrolumab can significantly reduce NET formation, improve cardiometabolic disease markers, and outperform placebo.
ARTHRITIS & RHEUMATOLOGY
(2021)
Article
Immunology
Cornelia D. Cudrici, Afroditi Boulougoura, Virginia Sheikh, Alexandra Freeman, Ornella Sortino, James D. Katz, Irini Sereti, Richard M. Siegel
Summary: This study characterized autoantibodies and autoimmune diseases in ICL patients, and found that evidence of autoimmunity, including autoimmune diseases, is more prevalent in ICL than in the general population. Patients with autoimmune disease had higher levels of serum immunoglobulins and more effector memory T cells.
CLINICAL IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Sarah S. Geiger, Javier Traba, Nathan Richoz, Taylor K. Farley, Stephen R. Brooks, Franziska Petermann, Lingdi Wang, Frank J. Gonzalez, Michael N. Sack, Richard M. Siegel
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Sarah S. Geiger, Javier Traba, Nathan Richoz, Taylor K. Farley, Stephen R. Brooks, Franziska Petermann, Lingdi Wang, Frank J. Gonzalez, Michael N. Sack, Richard M. Siegel
Summary: The time of day influences immune responses and lethality in response to LPS, with the highest survival rate at the beginning of the light cycle. Feeding, rather than light, is shown to control time-of-day dependent LPS sensitivity through liver clock and hepatic FXR signaling.
NATURE COMMUNICATIONS
(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)
Article
Cell Biology
Nicholas Frazzette, Anthony C. Cruz, Xufeng Wu, John A. Hammer, Jennifer Lippincott-Schwartz, Richard M. Siegel, Prabuddha Sengupta
Summary: This study found that interaction between Fas and membrane-bound FasL leads to rapid formation of Fas protein superclusters containing more than 20 receptors. It also showed that intact Fas death domain is essential for recruiting FADD. Furthermore, the study revealed the importance of Fas-FADD interaction in inducing apoptosis.
Article
Medicine, Research & Experimental
Nathan Richoz, Zewen K. Tuong, Kevin W. Loudon, Eduardo Patino-Martinez, John R. Ferdinand, Anais Portet, Kathleen R. Bashant, Emeline Thevenon, Francesca Rucci, Thomas Hoyler, Tobias Junt, Mariana J. Kaplan, Richard M. Siegel, Menna R. Clatworthy
Summary: In lupus nephritis, kidney macrophages show distinct division of labor, with TrMacs orchestrating leukocyte recruitment and MoMacs responsible for uptake and presentation of IC antigen.
Editorial Material
Cell Biology
Dominik Aschenbrenner, Richard M. Siegel
Summary: Lilja et al. investigate the single-cell transcriptomes of multiple organs in mice with collagen-induced arthritis. They prioritize functional pathways that either support or suppress inflammation using network analysis and integrate their findings with tissue transcriptomics in human immune-mediated inflammatory diseases.
CELL REPORTS MEDICINE
(2023)
Article
Medicine, Research & Experimental
Younglang Lee, Alex W. Wessel, Jiazhi Xu, Julia G. Reinke, Eries Lee, Somin M. Kim, Amy P. Hsu, Jevgenia Zilberman-Rudenko, Sha Cao, Clinton Enos, Stephen R. Brooks, Zuoming Deng, Bin Lin, Adriana A. de Jesus, Daniel N. Hupalo, Daniela G. P. Piotto, Maria T. Terreri, Victoria R. Dimitriades, Clifton L. Dalgard, Steven M. Holland, Raphaela Goldbach-Mansky, Richard M. Siegel, Eric P. Hanson
Summary: This study characterized a pediatric autoinflammatory syndrome called NEMO deleted exon 5 autoinflammatory syndrome (NDAS) in three unrelated male patients. The syndrome is caused by distinct X-linked IKBKG germline mutations that lead to overexpression of a NEMO protein isoform lacking the domain encoded by exon 5 (NEMO-Aex5). The patients exhibited increased NF-KB activation and IFN production in immune cells and blood cells.
JOURNAL OF CLINICAL INVESTIGATION
(2022)