The causal role of immune cells in primary Sjögren's syndrome: A two‐sample Mendelian randomization DOI
Yang Liu, Jie Kang, Yazhen Su

et al.

International Journal of Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 27(11)

Published: Nov. 1, 2024

Abstract Background Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by the destruction of exocrine glands primarily via T‐cell‐mediated B‐cell over‐activation and cytokine production. This leads to pronounced dryness mouth eyes can result in multi‐systemic involvement affecting kidneys, lungs, blood. In recent years, there has been increasing attention on role immune cells pSS. However, studies investigating causal pSS have relatively limited. Methods this study, we employed a two‐way two‐sample Mendelian randomization approach assess relationship between Utilizing publicly available genome‐wide association study (GWAS) data, explored links 731 immunophenotypically labeled risk Results Through use instrumental variables derived from GWAS data corrected for false discovery rate (FDR), identified three with increased levels that were causally associated (FDR < 0.05). These included IgD+ CD38br AC B cells, CD27 CD38− unswitched memory Granulocyte % leukocyte. Additionally, reduced found be risk, namely CD4+ CD8dim %lymphocyte, %leukocyte, CD28 activated secreting regulatory T (Tregs). Furthermore, development was elevated CD33br HLA DR+ CD14− myeloid cells. Conclusion demonstrates responses influence progression complex pattern. Our findings may provide new insights into immunology pathogenesis more experimental should conducted further explore potential mechanisms features which basis exploring early intervention methods developing targeted therapeutic strategies or even reshaping homeostasis.

Language: Английский

Defining immune reset: achieving sustained remission in autoimmune diseases DOI
Tobias Junt, Thomas Calzascia,

Elisabetta Traggiai

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

Citations

1
Targeting NF-kappaB-inducing kinase shapes B-cell homeostasis in myasthenia gravis DOI Creative Commons

Xiaoyu Huang,

Zhouao Zhang, Zhouyi Wang

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 24, 2025

B cell immune dysregulation plays a critical role in myasthenia gravis (MG). However, targeted B-cell therapy such as rituximab may result long-term peripheral clearance and allow for the survival of plasma cells, contributing to frequent infections relapses. Therefore, we aimed identify potential novel therapeutic targets that preserve part function while inhibiting antibody-secreting cells (ASCs). The transcriptome sorted CD19+B obtained from MG patients active remission state was performed by RNA sequencing. hallmark gene NF-kappaB-inducing kinase (NIK/MAP3K14) associated with NF-κB TNF signaling identified, expression levels NIK CD4+T serum new-onset controls were validated flow cytometry, qPCR ELISA. In vitro vivo, effects inhibitor (B022) on detected under PBMCs, experimental autoimmune (EAMG) rat model, respectively. upregulated patients. Notably, increased positively correlated disease severity decreased remission. B022 significantly reduced activation, proliferation, ASCs differentiation pathogenic function, well activation Th17 vitro. Intraperitoneal injection ameliorated EAMG rats, proportion T subsets, antibody postsynaptic membrane damage. Targeting small molecule inhibitors can effectively shape homeostasis, exhibit protective which be an effective treatment strategy MG.

Language: Английский

Citations

0
Proteome‐Wide Mendelian Randomization Identifies Candidate Causal Proteins for Cardiovascular Diseases DOI Creative Commons
Chen Li, Nicolas Jay, Shanshan Zhang

et al.

Advanced Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Integration of human genomics and other omics across different ancestries provides novel, affordable, systematic approach for target identification. We used Mendelian randomization approaches to unravel causal associations between 2,940 circulating proteins 19 CVD. found 218 that impacted risk one or more CVDs through forward MR (106 182 using cis‐pQTLs only cis‐ + trans‐pQTLs, respectively), among which 107 were previously reported as associated with CVD CVD‐related traits. There 102 replicated (FDR < 5%, 53 88 trans‐pQTLs) the FinnGen Olink data. BTN3A2 was highlighted a novel candidate gene ischemic stroke, suggesting crosstalk immune modulation stroke pathogenesis. Single cell integration prioritized PAM stable angina pectoris ventricular arrhythmia LPL peripheral artery disease, whose transcriptional expressions enriched in cardiomyocytes. Forward reverse largely non‐overlapping (only 2 overlapped: LGALS4 MMP12), distinct proteomic causes consequences Our study genetics‐based evidence genes, foundational step towards full‐scale biology‐based drug discovery

Language: Английский

Citations

0
Emerging roles of mechanically activated ion channels in autoimmune disease DOI

Zhiru Zeng,

Engeng Chen, Jing Xue

et al.

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: 24(7), P. 103813 - 103813

Published: April 7, 2025

Language: Английский

Citations

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Selenium-Binding Protein 1-Deficient Dendritic Cells Protect Mice from Sepsis by Increased Treg/Th17 DOI Creative Commons
Xin Zhang, Shuang Han,

Zhu Zeng

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 468 - 468

Published: April 14, 2025

Selenium-binding protein 1 (SELENBP1) has been implicated in cancer development, neurological disorders, tissue injury, metabolic regulation, and cell differentiation. Sepsis is characterized prominently by immunological dysregulation severe organ damage. However, whether SELENBP1 improves sepsis regulating immune activity remains unknown. Here, we detected an elevation of levels the blood patients livers septic mice. Significantly, knockout (KO) prolonged survival This phenomenon was accompanied decreased liver damage, reduced inflammation levels, increased regulatory T cell/T helper 17 (Treg/Th17) ratio spleen. Additionally, deficiency induced a redox imbalance inhibited dendritic (DC) maturation, resulting tolerogenic DC (tolDC) phenotype increase Treg/Th17 ratio. Furthermore, SELENBP1-KO mature DCs (mDCs) alleviated injury increasing spleen, thus improving These findings indicate that involved activity, which might provide potential way for treatment.

Language: Английский

Citations

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Depletion-restitution therapy for autoimmune rheumatic diseases. Part 1. Fundamental prerequisites and efficacy of modern treatment technologies: anti-B-cell drugs and CAR-T therapy DOI Creative Commons
А. М. Лила, А. L. Maslyanskiy, Д. А. Дибров

et al.

Modern Rheumatology Journal, Journal Year: 2025, Volume and Issue: 19(2), P. 7 - 17

Published: April 22, 2025

The key element in the pathogenesis of systemic autoimmune rheumatic diseases is breakdown immunological tolerance and formation a pool autoreactive cells. This leads to uncontrolled activation effector arm cellular (T-lymphocytes) humoral (B-lymphocytes plasma cells) immunity, proliferation clones, persistence memory In this process, T-cells, B-cells, cells memory, interaction with complex pathogenic signals from microenvironment, ensure stability adaptability developing inflammatory process. modern clinical practice, prevailing approach prescribing medications "therapeutic pyramid" strategy, which involves gradual escalation treatment until remission achieved. does not address mechanisms and, as result, requires lifelong therapy associated numerous adverse effects. term “depletion-restitution therapy” proposed (from English “depletion” – exhaustion; Latin “restitutio ad integrum” restoration original state, complete recovery) describe an alternative approach. characterized by methods based on massive, shortterm cytotoxic impact, leading profound reduction followed repopulation "naive" elements. Consequently, restores enables ultra-long, drug-free remissions. Currently, principles depletion-restitution have already been integrated into oncology, hematology, neurology. Among most promising potential targets for such rheumatology are effectors immune system: plasmablasts, At present stage, implementing CAR-T therapeutic bispecific monoclonal antibodies.

Language: Английский

Citations

0
Time for a paradigm shift in immunotherapy-based BCMA/CD3 bispecific drug development in multiple myeloma DOI
Xavier Leleu,

Arthur Bobin,

André Herbelin

et al.

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

Published: April 24, 2025

Language: Английский

Citations

0
The role of autoantibodies in bridging obesity, aging, and immunosenescence DOI Creative Commons
Taylor R. Valentino, Nan Chen, Priya Makhijani

et al.

Immunity & Ageing, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 30, 2024

Abstract Antibodies are essential to immune homeostasis due their roles in neutralizing pathogenic agents. However, failures central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance generate autoantibodies mistakenly target self-antigens, leading inflammation autoimmune diseases. While well-studied some communicable diseases, chronic conditions, such as obesity aging, less understood. Obesity aging share similar aspects of dysfunction, diminished humoral responses heightened inflammation, which disrupt tolerance foster autoantigen production, thus giving rise autoantibodies. In return, these events may also contribute the pathophysiology associated disorders linked development immunosenescence, an age-related decline function heightens vulnerability infections, loss self-tolerance. Furthermore, cumulative exposure antigens cellular debris during perpetuates pro-inflammatory pathways, linking immunosenescence with other hallmarks, proteostasis mitochondrial dysfunction. This review examines mechanisms driving autoantibody generation discusses key putative antigenic targets across conditions. We explore therapeutic potential emerging approaches, CAR-T/CAAR-T therapies, vaccines, BiTEs, tackle autoimmune-related conditions obesity.

Language: Английский

Citations

2
The essential roles of memory B cells in the pathogenesis of systemic lupus erythematosus DOI
Thomas Dörner, Peter E. Lipsky

Nature Reviews Rheumatology, Journal Year: 2024, Volume and Issue: 20(12), P. 770 - 782

Published: Nov. 7, 2024

Language: Английский

Citations

1
Ways to think about vasculitic neuropathy DOI
Mahima Kapoor, Stephen W. Reddel

Current Opinion in Neurology, Journal Year: 2024, Volume and Issue: 37(5), P. 478 - 486

Published: July 24, 2024

Purpose of review Vasculitis as a pathomechanism for neuropathy can be isolated to the peripheral nervous system, part systemic autoimmune condition or component another syndrome. This aims discuss broad range diagnoses in which vasculitic encountered, highlight progress imaging techniques identifying vasculitis, and new drugs developed other diseases that may applied neurological conditions. Recent findings Advances modalities, ultrasound, MRI FDG-PET scanning neuromuscular applications has redefined many aspects neuropathies. The benefit dividing vasculitides by vessel size is becoming less absolute diagnostic approaches advance. are widely used diagnosis, defining extent involvement disease monitoring. In neuralgic amyotrophy, identification hourglass-like constrictions on changed treatment paradigm include surgical interventions. These supported immunomodulating immunosuppression techniques. Summary Vasculitic neuropathies group conditions with causes associations. Increased use impacts our traditional definitions classifications. growth options likely infiltrate landscape.

Language: Английский

Citations

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