CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives DOI Creative Commons
Jincai Zhou,

Bixia Lei,

Feifei Shi

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Дек. 19, 2024

Systemic lupus erythematosus (SLE) and nephritis (LN) are debilitating autoimmune disorders characterized by pathological autoantibodies production immune dysfunction, causing chronic inflammation multi-organ damage. Despite current treatments with antimalarial drugs, glucocorticoids, immunosuppressants, monoclonal antibodies, a definitive cure remains elusive, highlighting an urgent need for novel therapeutic strategies. Recent studies indicate that chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in treating B-cell malignancies may offer significant breakthrough non-malignant conditions like SLE. In this paper, we aim to provide in-depth analysis of the advancements CAR-T SLE, focusing on its potential revolutionize treatment complex disease. We explore fundamental mechanisms cell action, rationale application immunological underpinnings also summarize clinical data safety efficacy anti-CD19 anti-B maturation (BCMA) cells targeting B-cells discuss implications these findings improve outcomes severe or refractory SLE cases. The integration into paradigm presents new horizon autoimmunity research practice. This review underscores continued exploration optimization strategies address unmet needs patients.

Язык: Английский

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus DOI Open Access
Daniele Accapezzato,

Rosalba Caccavale,

Maria Pia Paroli

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6578 - 6578

Опубликована: Март 31, 2023

Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE complex and involves cells both innate adaptive immunity. distinguishing feature the production autoantibodies, with formation immune complexes precipitate at vascular level, causing damage. Although progress understanding has been slower than other rheumatic diseases, new knowledge recently led to development effective targeted therapies, hold out hope for personalized therapy. However, drugs available date are still an adjunct conventional therapy, which known toxic short long term. purpose this review summarize recent advances disease discuss results obtained from use drugs, look future therapies may used absence current standard care or even cure serious systemic autoimmune disease.

Язык: Английский

Процитировано

72
Immunotherapy Strategy for Systemic Autoimmune Diseases: Betting on CAR-T Cells and Antibodies DOI Creative Commons
Vitaly Chasov,

Ekaterina Zmievskaya,

Irina Ganeeva

и другие.

Antibodies, Год журнала: 2024, Номер 13(1), С. 10 - 10

Опубликована: Фев. 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.

Язык: Английский

Процитировано

19
BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in systemic lupus erythematosus DOI Creative Commons
Quentin Moyon, Delphine Sterlin, Makoto Miyara

и другие.

Annals of the Rheumatic Diseases, Год журнала: 2021, Номер 81(4), С. 575 - 583

Опубликована: Окт. 4, 2021

Our aim was to evaluate systemic lupus erythematosus (SLE) disease activity and SARS-CoV-2-specific immune responses after BNT162b2 vaccination.In this prospective study, clinical assessments were recorded from the first dose of vaccine until day 15 second in 126 patients with SLE. SARS-CoV-2 antibody measured against wild-type spike antigen, while serum-neutralising assessed historical strain variants concerns (VOCs). Vaccine-specific T cell quantified by interferon-γ release assay dose.BNT162b2 well tolerated no statistically significant variations BILAG (British Isles Lupus Assessment Group) SLEDAI (SLE Disease Activity Index) scores observed throughout study SLE active inactive at baseline. Mycophenolate mofetil (MMF) methotrexate (MTX) treatments associated drastically reduced response (β=-78, p=0.007; β=-122, p<0.001, respectively). Anti-spike positively baseline total immunoglobulin G serum levels, naïve B frequencies (β=2, p=0.018; β=2.5, p=0.003) (r=0.462, p=0.003). In responders, neutralisation decreased VOCs bearing E484K mutation but remained detectable a majority patients.MMF, MTX poor humoral status, particularly low frequencies, are independently impaired mRNA response, delineating who might need adapted regimens follow-up.

Язык: Английский

Процитировано

77
Iron-dependent epigenetic modulation promotes pathogenic T cell differentiation in lupus DOI Creative Commons
Xiaofei Gao, Yang Song, Jiali Wu

и другие.

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(9)

Опубликована: Май 1, 2022

The trace element iron affects immune responses and vaccination, but knowledge of its role in autoimmune diseases is limited. Expansion pathogenic T cells, especially follicular helper (Tfh) has great significance to systemic lupus erythematosus (SLE) pathogenesis. Here, we show an important regulation cell differentiation SLE. We found that overload promoted Tfh expansion, proinflammatory cytokine secretion, autoantibody production lupus-prone mice. Mice treated with a high-iron diet exhibited increased proportion antigen-specific GC response. Iron supplementation contributed differentiation. In contrast, chelation inhibited demonstrated the miR-21/BDH2 axis drove accumulation during further Fe2+-dependent TET enzyme activity BCL6 gene demethylation. Thus, maintaining homeostasis might be critical for eliminating Th cells help improve management patients

Язык: Английский

Процитировано

56
Lipid Metabolism: Immune Regulation and Therapeutic Prospectives in Systemic Lupus Erythematosus DOI Creative Commons
Wei Sun, Pengchong Li,

Jianping Cai

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Март 18, 2022

Systemic lupus erythematosus (SLE) is a heterogeneous disease characterized by the production of abnormal autoantibodies and immune complexes that can affect organ systems, particularly kidneys cardiovascular system. Emerging evidence suggests dysregulated lipid metabolism, especially in key effector cells, such as T B innate exerts complex effects on pathogenesis progression SLE. Beyond their important roles membrane components energy storage, different lipids also modulate cellular processes, proliferation, differentiation, survival. In this review, we summarize altered metabolism associated mechanisms involved Furthermore, discuss recent progress role potential therapeutic target

Язык: Английский

Процитировано

48
IFN-γ, should not be ignored in SLE DOI Creative Commons
Wenping Liu, Shumin Zhang, Jibo Wang

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 10, 2022

Systemic lupus erythematosus (SLE) is a typical autoimmune disease with complex pathogenesis and genetic predisposition. With continued understanding of this disease, it was found that SLE related to the interferon gene signature. Most studies have emphasized important role IFN-α in SLE, but our previous study suggested nonnegligible IFN-γ SLE. Some scholars previously abnormally elevated as early before classification emergence autoantibodies IFN-α. Due large overlap between IFN-γ, mostly characterized by expression after onset. Therefore, may be underestimated. This article mainly reviews focuses on gain more comprehensive disease.

Язык: Английский

Процитировано

44
Systemic lupus erythematosus: latest insight into etiopathogenesis DOI Open Access

Akhil Akhil,

Rohit Bansal, Kumari Anupam

и другие.

Rheumatology International, Год журнала: 2023, Номер 43(8), С. 1381 - 1393

Опубликована: Май 24, 2023

Язык: Английский

Процитировано

32
The role of CD8+ T-cell systemic lupus erythematosus pathogenesis: an update DOI
Ping-Min Chen, George C. Tsokos

Current Opinion in Rheumatology, Год журнала: 2021, Номер 33(6), С. 586 - 591

Опубликована: Июнь 28, 2021

Purpose of review Systemic lupus erythematosus (SLE) is a serious autoimmune disease with wide range organ involvement. In addition to aberrant B-cell responses leading autoantibody production, T-cell abnormalities are important in the induction autoimmunity and ensuing downstream damage. this article, we present an update on how subsets CD8 + T cells contribute SLE pathogenesis. Recent findings Reduced cytolytic function not only promotes systemic but also accounts for increased risk infections. Additional information suggests that effector functions tissue The phenotypic changes likely arise from exposure microenvironment crosstalk resident cells. Research pathogenic IL-17-producing double negative their origin autoreactive cells, which maintenance autoimmunity. Summary illustrates role peripheral tolerance control Inflammatory cytokine producing functional defects regulatory cell both Further depth research these warranted development new therapeutics people SLE.

Язык: Английский

Процитировано

51
The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases DOI Creative Commons
Karolina Wojciechowicz, Marta Spodzieja, Katarzyna A. Lisowska

и другие.

Cellular Immunology, Год журнала: 2022, Номер 376, С. 104532 - 104532

Опубликована: Май 5, 2022

Autoimmune diseases constitute a heterogeneous group of disorders with one common feature - the loss immune tolerance towards autoantigens. Due to complexity pathogenesis these diseases, there are still many open questions regarding their etiology. Therefore, scientists unceasingly search for new data hoping detect dependable biomarkers and design safe effective treatment. The research on checkpoints is in line scientific clinical demands. Immune may be key understanding immunological disorders. BTLA-HVEM complex, inhibitory checkpoint, has recently caught attention as an important regulator different contexts, including autoreactivity. So far, complex been mainly studied context cancer, but numerous show, it also target treating autoimmune diseases. In this review, we intend focus mechanisms interactions cells summarize available autoimmunity.

Язык: Английский

Процитировано

33
Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus DOI Creative Commons
Kavita Y. Sarin, Hong Zheng, Yashaar Chaichian

и другие.

JCI Insight, Год журнала: 2024, Номер 9(5)

Опубликована: Март 8, 2024

Understanding the immune responses to SARS-CoV-2 vaccination is critical optimizing strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive in 19 patients SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared control cohort of 56 healthy (HC) volunteers. Patients exhibited impaired neutralizing antibody production antigen-specific CD4+ CD8+ T cell relative HC. Interestingly, were only altered treated immunosuppressive therapies, whereas impairment numbers was independent medication. also displayed reduced levels circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, IFN-γ after secondary well downregulation gene expression pathways indicative compromised responses. Single-cell RNA-Seq analysis reveals that showed vaccine-inducible monocyte population characterized by overexpression IFN-response transcription factors. Thus, although 2 doses BNT162b2 induced relatively robust SLE, our data demonstrate both HC, highlighting need population-specific studies.

Язык: Английский

Процитировано

9