Interferon signature in the development of SLE: molecular mechanisms, approaches to diagnosis and treatment DOI Creative Commons

TO Nakonechnaya,

Irina A. Shagina,

M.Y. Myshkin

et al.

Bulletin of Russian State Medical University, Journal Year: 2024, Volume and Issue: 2024(3)

Published: June 1, 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation of connective tissue and damage to various organs, including joints, skin, kidneys heart. The has significant gender predisposition more common in women. pathogenesis SLE based on violation immunological tolerance, accompanied activation B lymphocytes the production autoantibodies. Recent advances basic research have significantly deepened understanding immunopathogenetic mechanisms SLE, which justifies use new pharmacotherapeutic approaches. These approaches involve biological drugs aimed at blocking activity type I interferon (IFN) or its receptors. article discusses molecular response modern methods for diagnosing signature, treatment pathway. possible role signature stratification patients also discussed. Such will make it effective select regimens taking into account individual characteristics immune each patient. This may increase effectiveness treatment, reduce likelihood side effects improve prognosis with SLE.

Language: Английский

Immunotherapy Strategy for Systemic Autoimmune Diseases: Betting on CAR-T Cells and Antibodies DOI Creative Commons
Vitaly Chasov,

Ekaterina Zmievskaya,

Irina Ganeeva

et al.

Antibodies, Journal Year: 2024, Volume and Issue: 13(1), P. 10 - 10

Published: Feb. 1, 2024

Systemic autoimmune diseases (SAIDs), such as systemic lupus erythematosus (SLE), sclerosis (SSc) and rheumatoid arthritis (RA), are fully related to the unregulated innate adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics, including interferon signature, loss of tolerance self-nuclear antigens, enhanced tissue damage like necrosis fibrosis. Glucocorticoids immunosuppressants, which limited specificity prone tolerance, used first-line therapy. A plethora novel immunotherapies been developed, monoclonal bispecific antibodies, other biological agents target cellular soluble factors disease pathogenesis, B cells, co-stimulatory molecules, cytokines or receptors, signaling molecules. Many these shown encouraging results clinical trials. CAR-T cell therapy is considered most promising technique for curing diseases, with recent successes treatment SLE SSc. Here, we overview therapeutic approaches based on cells antibodies targeting diseases.

Language: Английский

Citations

18
Clinical and laboratory characteristics of early-onset and delayed-onset lupus nephritis patients: A single-center retrospective study DOI Creative Commons
Joanna Kosałka-Węgiel, Radosław Dziedzic, Andżelika Siwiec-Koźlik

et al.

Rheumatology International, Journal Year: 2024, Volume and Issue: 44(7), P. 1283 - 1294

Published: March 28, 2024

Abstract Background Lupus nephritis (LN) manifests systemic lupus erythematosus (SLE) and is characterized by various clinical laboratory features. This study aimed to comprehensively evaluate the characteristics of LN patients according time diagnosis: early-onset (LN diagnosed within one year from SLE diagnosis) vs. delayed-onset more than after diagnosis). Methods We conducted a retrospective analysis medical records all treated at University Hospital in Kraków, Poland, 2012 2022. collected data on demographic, clinical, characteristics, including histological findings, treatment modalities, disease outcomes. Statistical analyses were performed identify factors impacting development prognosis. Results Among 331 patients, was 207 (62.54%) documented 122 cases (36.86%). In 2 (0.6%) cases, first kidney manifestation course unknown. Delayed-onset had higher female-to-male ratio younger age diagnosis. group associated with severe manifestations. turn, studied subgroups did not differ internist comorbidities, histopathology, family history regarding autoimmune diseases. exhibited frequency anti-dsDNA, anti-Smith, anti-Ro, anti-RNP, anti-cardiolipin IgG autoantibodies. During 14-year follow-up period, 16 died. Mortality rate causes death comparable both analyzed subgroups. Conclusions More manifestations prompt strict monitoring non-LN diagnose treat involvement early. Also, recognizing autoantibodies such as anti-dsDNA or anti-Smith underscores potential value autoantibody profiling diagnostic prognostic tool.

Language: Английский

Citations

10
Regulatory T Cells and Their Derived Cell Pharmaceuticals as Emerging Therapeutics Against Autoimmune Diseases DOI
Yu Liu,

Yiqiu Fu,

Rourou Miao

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: July 6, 2024

Abstract Caused by the loss in tolerance against self‐antigens, autoimmune diseases are chronic disorders that impact millions of individuals annually with significant economic burden. They triggered a deficiency quantity or function regulatory T (Treg) cells, which essential for maintaining self‐tolerance and preventing excessive immune responses. Several clinical trials over past decade have demonstrated safety feasibility certain Treg cell‐based therapies diseases, inspiring optimism among patients. Studies indicated targeted cell pharmaceuticals significantly promising, offering superior targeting, improved biocompatibility, prolonged blood circulation. Thus, delivery systems also extensively studied. This review describes role cells system both homeostasis development autoimmunity, purification expansion methods, derived pharmaceutical therapies, therapeutic potential beneficial to accelerating industrialization translation formulations based on cells.

Language: Английский

Citations

5
Upregulated TCF1+ Treg Cells With Stronger Function in Systemic Lupus Erythematosus Through Activation of the Wnt‐β‐Catenin DOI Open Access

Xingyue Zeng,

Yiming Gao,

Ayibaota Bahabayi

et al.

Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

The role of T-cell factor 1 (TCF1) in human regulatory T cells (Treg) and its clinical significance systemic lupus erythematosus (SLE) remain unclear. Through bioinformatics analysis flow cytometry, the Tcf7 gene TCF1 protein were found to be highly expressed Treg cells. TCF1+ exhibited increased expression CTLA4 LAG3 higher IL-10 secretion than TCF1- Circulating elevated displayed inhibitory markers SLE patients. Wnt-β-catenin pathway was activated addition XAV939 impaired function Clinically, not only related CRP, ESR IL-2, but also could differentiate patients from healthy controls, primary Sjögren's syndrome rheumatoid arthritis In conclusion, indicate a stronger suppressive for help screening assisting diagnosis

Language: Английский

Citations

0
Revisiting Migraine Pathophysiology: from Neurons To Immune Cells Through Lens of Immune Regulatory Pathways DOI

Sugumar Subalakshmi,

Rapuru Rushendran, Chitra Vellapandian

et al.

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: April 2, 2025

Language: Английский

Citations

0
Identification of cellular senescence-related genes as biomarkers for lupus nephritis based on bioinformatics DOI Creative Commons
Wei Chen, Xiaofang Wang,

Guoshun Huang

et al.

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Background Lupus nephritis (LN) is one of the most common and severe complications systemic lupus erythematosus with unclear pathogenesis. The accurate diagnosis criterion LN still renal biopsy nowadays treatment strategies are far from satisfactory. Cellular senescence defined as permanent cell cycle arrest marked by senescence-associated secretory phenotype (SASP), which has been proved to accelerate mobility mortality patients LN. study aimed identify cellular senescence-related genes for Methods Genes related were obtained MSigDB genetic database GEO respectively. Through differential gene analysis, Weighted Gene Go-expression Network Analysis (WGCNA) machine learning algorithms, hub differentially expressed (CS-DEGs) identified. By external validation, CS-DEGs further filtered remaining identified biomarkers. We explored their potential physiopathologic function through GSEA. Results 432 senescence, 1,208 (DEGs) 840 in key module LN, intersected each other CS-DEGs. Subsequent Machine algorithms screened out six finally three CS-DEGs, ALOX5, PTGER2 PRKCB passed biomarkers enriched “B Cell receptor signaling pathway” “NF−kappa B based on GESA results. Conclusion This relationship between PTGER2, playing roles will provide new insights

Language: Английский

Citations

0
Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation DOI Open Access
Vitaly Chasov,

Ekaterina Zmievskaya,

Irina Ganeeva

et al.

Journal of Biomedical Research, Journal Year: 2024, Volume and Issue: 38(6), P. 531 - 531

Published: Jan. 1, 2024

Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of the innate and adaptive immune systems, leading to an attack on healthy tissues body. During development SLE, pathogenic features, such as formation autoantibodies self-nuclear antigens, caused tissue damage including necrosis fibrosis, with increased expression type Ⅰ interferon (IFN) regulated genes. Treatment immunosuppressants glucocorticoids, which are used standard therapy, not effective enough causes side effects. As alternative, more immunotherapies have been developed, monoclonal bispecific antibodies that target B cells, T co-stimulatory molecules, cytokines or their receptors, signaling molecules. Encouraging results observed in clinical trials some these therapies. Furthermore, chimeric antigen receptor cells (CAR-T) therapy has emerged most effective, safe, promising treatment option for demonstrated successful pilot studies. Additionally, emerging evidence suggests gut microbiota dysbiosis may play significant role severity use methods normalize microbiota, particularly fecal transplantation (FMT), opens up new opportunities SLE.

Language: Английский

Citations

3
Epigenetic regulation of immune cells in systemic lupus erythematosus: insight from chromatin accessibility DOI

Zhao‐Xing Gao,

He Tian, Peng Zhang

et al.

Expert Opinion on Therapeutic Targets, Journal Year: 2024, Volume and Issue: 28(7), P. 637 - 649

Published: June 29, 2024

Introduction Systemic Lupus Erythematosus (SLE) is a multi-dimensional autoimmune disease involving numerous tissues throughout the body. The chromatin accessibility landscapes in immune cells play pivotal role governing their activation, function, and differentiation. Aberrant modulation of intimately associated with onset progression SLE.

Language: Английский

Citations

2
Deciphering Regulatory T-Cell Dynamics in Cancer Immunotherapy: Mechanisms, Implications, and Therapeutic Innovations DOI
Sankha Bhattacharya,

Gaurav Paraskar,

Megha Jha

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(8), P. 2215 - 2236

Published: July 3, 2024

This Review explores how tumor-associated regulatory cells (Tregs) affect cancer immunotherapy. It shows Tregs play a role in keeping the immune system check, cancers grow, and well immunotherapy work. use many ways to suppress system, these are affected by tumor microenvironment (TME). New approaches therapy showing promise, such as targeting Treg checkpoint receptors precisely using Fc-engineered antibodies. is important tailor treatments each patient's TME order provide personalized care. Understanding biology essential for creating effective improving long-term outcomes of

Language: Английский

Citations

2
Progress of rituximab in the treatment of systemic lupus erythematosus and lupus nephritis DOI Creative Commons

Shouqi Mo,

Yilan Li,

Junbing He

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 4, 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with heterogeneous clinical manifestations, often leading to significant morbidity and mortality, particularly due nephritis (LN). The standard therapeutic approach involving mycophenolate mofetil, cyclophosphamide, glucocorticoids has shown limitations cumulative toxicity side effects. introduction of biologic agents, especially rituximab (RTX), chimeric monoclonal antibody targeting CD20+ B cells, revolutionized the treatment landscape. This review synthesized current understanding cells’ role in SLE LN evaluates RTX’s impact. cells contribute pathogenesis through autoantibody production immune complex formation, tissue damage. mechanisms action, including Complement-Dependent cytotoxicity (CDC), antibody-dependent cell-mediated (ADCC), induction apoptosis, have demonstrated efficacy both treatment. Clinical studies reported remission rates improved renal outcomes RTX use, although challenges such as human anti-chimeric development optimal dosing persist. emphasized need for continued research elucidate long-term benefits risks, explore personalized strategies that incorporate cell biology better management LN.

Language: Английский

Citations

2