keyword
https://read.qxmd.com/read/38124132/the-crucial-regulatory-role-of-type-i-interferon-in-inflammatory-diseases
#21
REVIEW
Ling Ji, Tianle Li, Huimin Chen, Yanqi Yang, Eryi Lu, Jieying Liu, Wei Qiao, Hui Chen
Type I interferon (IFN-I) plays crucial roles in the regulation of inflammation and it is associated with various inflammatory diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and periodontitis, impacting people's health and quality of life. It is well-established that IFN-Is affect immune responses and inflammatory factors by regulating some signaling. However, currently, there is no comprehensive overview of the crucial regulatory role of IFN-I in distinctive pathways as well as associated inflammatory diseases...
December 20, 2023: Cell & Bioscience
https://read.qxmd.com/read/38123459/burden-of-systemic-lupus-erythematosus-in-clinical-practice-baseline-data-from-the-sle-prospective-observational-cohort-study-spocs-by-interferon-gene-signature
#22
JOURNAL ARTICLE
Laurent Arnaud, Richard Furie, Eric F Morand, Martin Aringer, Christine Peschken, Barnabas Desta, Eleni Rapsomaniki, Jonatan Hedberg, Jacob Knagenhjelm, Caroline Seo, Tina Grünfeld Eén, Alessandro Sorrentino, Raj Tummala, Heide A Stirnadel-Farrant, Bo Ding
OBJECTIVE: The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity. METHODS: SPOCS (NCT03189875) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria...
December 20, 2023: Lupus Science & Medicine
https://read.qxmd.com/read/38123338/unmet-need-in-rheumatology-reports-from-the-advances-in-targeted-therapies-meeting-2023
#23
JOURNAL ARTICLE
Kevin L Winthrop, Philip Mease, Andreas Kerschbaumer, Reinhard E Voll, Ferdinand C Breedveld, Josef S Smolen, Jacques-Eric Gottenberg, Xenofon Baraliakos, Hans P Kiener, Daniel Aletaha, John D Isaacs, Maya H Buch, Mary K Crow, Jonathan Kay, Leslie Crofford, Ronald F van Vollenhoven, Caroline Ospelt, Stefan Siebert, Margreet Kloppenburg, Iain B McInnes, Tom Wj Huizinga, Ellen M Gravallese
The Advances in Targeted Therapies meets annually, convening experts in the field of rheumatology to both provide scientific updates and identify existing scientific gaps within the field. To review the major unmet scientific needs in rheumatology. The 23rd annual Advances in Targeted Therapies meeting convened with more than 100 international basic scientists and clinical researchers in rheumatology, immunology, infectious diseases, epidemiology, molecular biology and other specialties relating to all aspects of immune-mediated inflammatory diseases...
December 20, 2023: Annals of the Rheumatic Diseases
https://read.qxmd.com/read/38114267/case-series-of-anifrolumab-for-treatment-of-cutaneous-lupus-erythematosus-and-lupus-related-mucocutaneous-manifestations-in-patients-with-sle
#24
JOURNAL ARTICLE
Aaron Bao, Michelle A Petri, Andrea Fava, Jun Kang
OBJECTIVE: To assess the efficacy of anifrolumab, a type-1 interferon receptor subunit-1 monoclonal antibody, in treating refractory cutaneous lupus erythematosus (CLE) and lupus non-specific mucocutaneous manifestations in patients with systemic lupus erythematosus (SLE). METHODS: A case series comprising four SLE patients with refractory CLE received anifrolumab (300mg) as add-on therapy. Medical history, serological markers and images were collected. Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) was assessed at baseline and post-treatment visits...
December 19, 2023: Lupus Science & Medicine
https://read.qxmd.com/read/38077311/endosomal-trafficking-inhibitor-ega-can-control-tlr7-mediated-ifn%C3%AE-expression-by-human-plasmacytoid-dendritic-cells
#25
JOURNAL ARTICLE
Matthew J Wiest, Laurie Baert, Chao Gu, Kevin M Gayler, Hyoungjun Ham, Laurent Gorvel, Mira T Keddis, Leroy W Griffing, HyeMee Joo, Jean-Pierre Gorvel, Daniel D Billadeau, Robert R Kane, SangKon Oh
Plasmacytoid dendritic cells (pDC) are the major producer of type 1 IFN in response to TLR7 agonists. Aberrant TLR7 activation and type 1 IFN expression by pDCs are linked to the pathogenesis of certain types of autoimmune diseases, including systemic lupus erythematosus (SLE). This study investigated the underlying mechanisms for TLR7-mediated cytokine expression by pDCs using a late endosome trafficking inhibitor, EGA (4-bromobenzaldehyde N -(2,6-dimethylphenyl) semicarbazone). We found that EGA treatment decreased IFNα expression by pDCs stimulated with imiquimod (R837), single-stranded RNA40, and influenza virus...
2023: Frontiers in Immunology
https://read.qxmd.com/read/38076936/cell-specific-transposable-element-gene-expression-analysis-identifies-associations-with-systemic-lupus-erythematosus-phenotypes
#26
Zachary Cutts, Sarah Patterson, Lenka Maliskova, Kimberly E Taylor, Chun Ye, Maria Dall'Era, Jinoos Yazdany, Lindsey Criswell, Gabriela K Fragiadakis, Charles Langelier, John A Capra, Marina Sirota, Cristina M Lanata
There is an established yet unexplained link between interferon (IFN) and systemic lupus erythematosus (SLE). The expression of sequences derived from transposable elements (TEs) may contribute to production of type I IFNs and generation of autoantibodies. We profiled cell-sorted RNA-seq data (CD4+ T cells, CD14+ monocytes, CD19+ B cells, and NK cells) from PBMCs of 120 SLE patients and quantified TE expression identifying 27,135 TEs. We tested for differential TE expression across 10 SLE phenotypes including autoantibody production and disease activity and discovered 731 differentially expressed (DE) TEs whose effects were mostly cell-specific and phenotype-specific...
November 28, 2023: bioRxiv
https://read.qxmd.com/read/38073566/sle-criteria-are-by-necessity-still-based-on-clinical-and-immunological-criteria-items
#27
REVIEW
Martin Aringer, Marta Mosca
INTRODUCTION: The 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) rely on clinical and routine immunological items. The criteria have anti-nuclear antibodies (ANA) as an obligatory entry criterion; items are weighted and ordered in domains. While demonstrating good sensitivity and specificity, the lack of a more molecular approach to some came as a disappointment. AREAS COVERED: Based on a non-systematic literature search, this review covers items investigated in the EULAR/ACR classification criteria project, but not included in the set of criteria...
December 11, 2023: Expert Review of Clinical Immunology
https://read.qxmd.com/read/38009863/role-of-neutrophils-in-cutaneous-lupus-erythematosus
#28
REVIEW
Toshiyuki Yamamoto
There are various types of cutaneous lupus erythematosus (CLE), either with or without the association of systemic lupus erythematosus (SLE). In some of the subtypes of cutaneous lupus, histopathology reveals neutrophil infiltration in the lesional skin; however, the significance of neutrophils in CLE is not yet fully elucidated. Recent studies have shown that neutrophil extracellular traps (NETs) formation by activated neutrophils is observed in several types of CLE, including lupus panniculitis, subacute lupus erythematosus, and acute lupus erythematosus, although the number of reports is small...
November 27, 2023: Journal of Dermatology
https://read.qxmd.com/read/38003689/an-emerging-role-for-anti-dna-antibodies-in-systemic-lupus-erythematosus
#29
REVIEW
Tetsuo Kubota
Anti-DNA antibodies are hallmark autoantibodies produced in systemic lupus erythematosus (SLE), but their pathogenetic role is not fully understood. Accumulating evidence suggests that some anti-DNA antibodies enter different types of live cells and affect the pathophysiology of SLE by stimulating or impairing these cells. Circulating neutrophils in SLE are activated by a type I interferon or other stimuli and are primed to release neutrophil extracellular traps (NETs) on additional stimulation. Anti-DNA antibodies are also involved in this process and may induce NET release...
November 19, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37965329/expansion-of-extrafollicular-b-and-t-cell-subsets-in-childhood-onset-systemic-lupus-erythematosus
#30
JOURNAL ARTICLE
Ryan M Baxter, Christine S Wang, Josselyn E Garcia-Perez, Daniel S Kong, Brianne M Coleman, Valentyna Larchenko, Ronald P Schuyler, Conner Jackson, Tusharkanti Ghosh, Pratyaydipta Rudra, Debdas Paul, Manfred Claassen, Rosemary Rochford, John C Cambier, Debashis Ghosh, Jennifer C Cooper, Mia J Smith, Elena W Y Hsieh
INTRODUCTION: Most childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%. Thus, there is urgent need to decipher and target immune mechanisms that drive cLN. Despite the clear role of autoantibody production in SLE, targeted B cell therapies such as rituximab (anti-CD20) and belimumab (anti-BAFF) have shown only modest efficacy in cLN...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37946666/single-cell-profiling-of-bone-marrow-b-cells-uncovers-early-b-cell-developmental-disorders-associated-with-systemic-lupus-erythematosus
#31
JOURNAL ARTICLE
Chen Dong, Yicheng Guo, Zechuan Chen, Teng Li, Juan Ji, Chi Sun, Jing Li, Haixia Cao, Yunfei Xia, Zhonghui Xue, Xixi Gu, Qian Liang, Rui Zhao, Ting Fu, Jiaqiang Ma, Shan Jiang, Chunmei Wu, Qiong Fu, Genkai Guo, Yanfeng Bao, Hua Guo, Junling Yang, Min Xu, Xiaoming Zhang, Zizhang Sheng, Zhifeng Gu
OBJECTIVE: The peripheral B cell compartment is heavily disturbed in systemic lupus erythematosus (SLE), but whether B cells develop aberrantly in the bone marrow (BM) is largely unknown. METHODS: We performed single-cell RNA/B cell receptor (BCR) sequencing and immune profiling of BM B cells and classified SLE patients into two groups: early B cell (Pro-B and Pre-B) normal (EBnor ) and EB defective/low (EBlo ) groups. RESULTS: The SLE-EBlo group exhibited more severe disease activity and proinflammatory status, overaction of type I interferon signaling and metabolic pathways within the B cell compartment, and aberrant BCR repertoires compared with the SLE-EBnor group...
November 10, 2023: Arthritis & Rheumatology
https://read.qxmd.com/read/37940417/fumarate-hydratase-as-a-metabolic-regulator-of-immunity
#32
REVIEW
Christian G Peace, Shane M O'Carroll, Luke A J O'Neill
Tricarboxylic acid (TCA) cycle metabolites have been implicated in modulating signalling pathways in immune cells. Notable examples include succinate and itaconate, which have pro- and anti-inflammatory roles, respectively. Recently, fumarate has emerged as having specific roles in macrophage activation, regulating the production of such cytokines as interleukin (IL)-10 and type I interferons (IFNs). Fumarate hydratase (FH) has been identified as a control point. Notably, FH loss in different models and cell types has been found to lead to DNA and RNA release from mitochondria which are sensed by cytosolic nucleic acid sensors including retinoic acid-inducible gene (RIG)-I, melanoma differentiation-associated protein (MDA)5, and cyclic GMP-AMP synthase (cGAS) to upregulate IFN-β production...
November 6, 2023: Trends in Cell Biology
https://read.qxmd.com/read/37933302/synergistic-effects-of-azithromycin-and-sting-agonist-promote-ifn-i-production-by-enhancing-the-activation-of-sting-tbk1-signaling
#33
JOURNAL ARTICLE
Kanoktip Petcharat, Narongsuk Munkong, Rungthip Thongboontho, Widsanusan Chartarrayawadee, Arthid Thim-Uam
BACKGROUND: Azithromycin (AZM) is a macrolide antibiotic that exhibits anti-inflammatory and anti-viral infection properties by enhancing type-I interferon (IFN-I) responses. The stimulator of interferon genes (STING) can directly induce IFN-I production. However, elevated IFN-I induces auto-immune phenotypes such as systemic lupus erythematosus (SLE). The effects of AZM and STING on the production of IFN-I are unclear. OBJECTIVE: Therefore, this study aims to evaluate the role of AZM and STING on IFN-I responses in macrophages...
2023: Journal of Experimental Pharmacology
https://read.qxmd.com/read/37901251/mitochondrial-antiviral-signaling-protein-a-potential-therapeutic-target-in-renal-disease
#34
REVIEW
Meng Wu, Zhiyin Pei, Guangfeng Long, Hongbing Chen, Zhanjun Jia, Weiwei Xia
Mitochondrial antiviral signaling protein (MAVS) is a key innate immune adaptor on the outer mitochondrial membrane that acts as a switch in the immune signal transduction response to viral infections. Some studies have reported that MAVS mediates NF-κB and type I interferon signaling during viral infection and is also required for optimal NLRP3 inflammasome activity. Recent studies have reported that MAVS is involved in various cancers, systemic lupus erythematosus, kidney diseases, and cardiovascular diseases...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37891416/b-cell-phenotype-and-serum-levels-of-interferons-baff-and-april-in-multisystem-inflammatory-syndrome-in-children-associated-with-covid-19-mis-c
#35
JOURNAL ARTICLE
Adam Klocperk, Marketa Bloomfield, Zuzana Parackova, Ludovic Aillot, Jiri Fremuth, Lumir Sasek, Jan David, Filip Fencl, Aneta Skotnicova, Katerina Rejlova, Martin Magner, Ondrej Hrusak, Anna Sediva
BACKGROUND: Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after the original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia, and activation of T cells with elevated IFN-γ. Observing the production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II, and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19...
October 28, 2023: Molecular and Cellular Pediatrics
https://read.qxmd.com/read/37877249/the-development-of-litifilimab-biib-059-for-cutaneous-and-systemic-lupus-erythematosus
#36
REVIEW
Young Min Cho, Richard Furie
This review describes the litifilimab (BIIB 059) development program to date for systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). Plasmacytoid dendritic cells (pDCs), major producers of type I interferons (IFN-I), play a key role in SLE pathogenesis. Litifilimab, a humanized monoclonal antibody, binds to BDCA2, a protein uniquely expressed on pDCs. The consequence of BDCA2 ligation is the inhibition of IFN-I as well as IFN-III, cytokine and chemokine production. Phase I and II LILAC trial parts A and B achieved primary end points in SLE and CLE patients, confirming the importance of pDCs and IFN-I in SLE and CLE...
October 25, 2023: Immunotherapy
https://read.qxmd.com/read/37860982/emerging-immunotherapeutic-strategies-for-cutaneous-lupus-erythematosus-an-overview-of-recent-phase-2-and-3-clinical-trials
#37
REVIEW
Darosa Lim, Julianne Kleitsch, Victoria P Werth
INTRODUCTION: Cutaneous lupus erythematosus (CLE) is an autoimmune disease that is clinically heterogenous and may occur with or without the presence of systemic lupus erythematosus (SLE). While existing on a spectrum, CLE and SLE present differences in their underlying pathogenesis and therapeutic responses. No new therapies have been approved in recent decades by the U.S. Food and Drug Administration for CLE, although frequently refractory to conventional therapies. There is an unmet need to develop effective drugs for CLE as it significantly impacts patients' quality of life and may leave irreversible disfiguring damage...
October 20, 2023: Expert Opinion on Emerging Drugs
https://read.qxmd.com/read/37809086/case-report-response-of-cutaneous-lupus-lesions-in-sle-to-interferon-receptor-blockade-parallels-reduction-of-interferon-score-in-blood
#38
Claudia Günther, Christine Wolf, Louisa Fennen, Sarah Rösing, Stefan Beissert, Martin Aringer, Min Ae Lee-Kirsch
Cutaneous lupus erythematosus (CLE), the main manifestation of systemic lupus erythematosus (SLE), is driven by type I interferons (IFNs) and often only partially responds to conventional therapies. Treatment of seven SLE patients with the monoclonal antibody anifrolumab induced fast and sustained remission of previously refractory CLE lesions, beginning within the first weeks of treatment. Decline in CLASI-A score was paralleled by a reduction in IFN score determined by mRNA expression of seven IFN-stimulated genes (ISGs) in blood...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37804401/imatinib-and-m351-0056-enhance-the-function-of-vista-and-ameliorate-the-development-of-sle-via-ifn-i-and-noncanonical-nf-%C3%AE%C2%BAb-pathway
#39
JOURNAL ARTICLE
Lu Yang, Tingting Zhang, Penglu Wang, Wenting Chen, Wanmei Liu, Xiaoyu He, Yuxin Zhang, Shasha Jin, Zhijie Luo, Zunjian Zhang, Xinzhi Wang, Jun Liu
V-domain immunoglobulin suppressor of T-cell activation (VISTA), an important negative checkpoint protein, participates in immunoregulation. Systemic lupus erythematosus (SLE) is an autoimmune disease in which patients exhibit high levels of autoantibodies and multi-organ tissue injury, primarily involving the kidney and skin. In wild-type (WT) mice and Vsir-/- mice with pristane-induced lupus-like disease, we found that VISTA deficiency exacerbated the lupus-like disease in mice, possibly through aberrant activation of type I interferon (IFN-I) signaling, CD4+ T cell, and noncanonical nuclear factor-κB (NF-κB) pathway...
October 7, 2023: Cell Biology and Toxicology
https://read.qxmd.com/read/37800604/anifrolumab-first-biologic-approved-in-the-eu-not-restricted-to-patients-with-a-high-degree-of-disease-activity-for-the-treatment-of-moderate-to-severe-systemic-lupus-erythematosus
#40
REVIEW
Noémie Gensous, Estibaliz Lazaro, Patrick Blanco, Christophe Richez
INTRODUCTION: Type 1 interferons (IFNs) play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) and various type I IFNs targeting therapeutic approaches have been developed. Anifrolumab, a monoclonal antibody that binds to the subunit 1 of the type I IFN receptor, has acquired considerable interest and has entered different clinical human trials willing to evaluate its efficacy and safety. AREAS COVERED: This review summarizes the data obtained in phases 1, 2, and 3 clinical trials of anifrolumab for SLE patients...
October 6, 2023: Expert Review of Clinical Immunology
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