系统性红斑狼疮:从发病机制到新型靶向治疗

沈田; 吴小川

doi:10.12290/xhyxzz.2022-0694

系统性红斑狼疮:从发病机制到新型靶向治疗

doi: 10.12290/xhyxzz.2022-0694

沈田,
吴小川^,

中南大学湘雅二医院儿科, 长沙 410011

基金项目:

国家自然科学基金青年科学基金(82101905)

国家重点研发计划(2021YFC2702004)

详细信息

通讯作者:
吴小川,E-mail:xiaochuanwu@csu.edu.cn

中图分类号: R593.2
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- 文章访问数: 37
- HTML全文浏览量: 7
- PDF下载量: 26
- 被引次数: 0
出版历程
- 收稿日期: 2022-12-05
- 网络出版日期: 2023-03-14

Systemic Lupus Erythematosus: From Pathogenesis to New Targeted Therapies

SHEN Tian,
WU Xiaochuan^,

Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China

Funds:

National Natural Science Foundation of China Youth Project(82101905)

National Key Research and Development Program of China (2021YFC2702004)

摘要

摘要: 系统性红斑狼疮是一种累及多器官/系统的自身免疫性疾病,其病因复杂,涉及分子遗传、表观遗传、先天性免疫、获得性免疫、种族、激素和环境因素等多个方面。近年来,随着免疫细胞的精细分型、全基因组关联研究、单细胞测序、多组学分析、基因编辑等技术的推广应用,人们对SLE的发病机制有了越来越深入的认识,也推动了各种靶向免疫细胞、共刺激分子、细胞因子/信号转导通路的单克隆抗体或小分子药物以及嵌合抗原受体T细胞免疫治疗的开发及临床研究。贝利尤单抗、泰它西普、阿尼鲁单抗以及伏环孢素获批应用于SLE为中重度SLE患者,尤其是难治性SLE患者提供了更多可选策略。
- 系统性红斑狼疮 /
- 发病机制 /
- 生物制剂 /
- 靶向治疗
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs or systems. The etiology of SLE is complex, involving molecular genetics, epigenetics, innate immunity, acquired immunity, race, hormone and environmental factors. Recent progress in fine immunophenotyping, GWAS, single cell sequencing and multiomics analysis has enabled a deeper understanding of the pathogenesis of SLE. Various monoclonal antibodies or small molecule drugs targeting immune cells, costimulatory molecules, cytokines or signal transduction pathways, and CART cell immunotherapy have been developed or even applied in clinical treatment. The approval of belizumab, telitacicept,anifrolumab and voclosporin for SLE has given clinicians, researchers and patients greater confidence and more treatment options for patients with moderate to severe SLE, especially those with refractory SLE.
- systemic lupus erythematosus /
- pathogenesis /
- biological agents /
- targeted therapy

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参考文献(48)

[1]	Unlu B, Tursen U, Jabalameli N, et al. Immunogenetics of Lupus Erythematosus[J]. Adv Exp Med Biol,2022,1367:213-257.
[2]	Wang YF, Zhang Y, Lin Z, et al. Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups[J]. Nat Commun,2021,12:772.
[3]	Wang M, Peng Y, Li H, et al. From monogenic lupus to TLR7/MyD88-targeted therapy[J]. Innovation (Camb),2022,3:100299.
[4]	Shi F, Xue R, Zhou X, et al. Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease[J]. Immunopharmacol Immunotoxicol,2021,43:666-673.
[5]	Parra Sanchez AR, Voskuyl AE, van Vollenhoven RF. Treat-to-target in systemic lupus erythematosus:advancing towards its implementation[J]. Nat Rev Rheumatol,2022,18:146-157.
[6]	Ameer MA, Chaudhry H, Mushtaq J, et al. An Overview of Systemic Lupus Erythematosus (SLE) Pathogenesis, Classification, and Management[J]. Cureus,2022,14:e30330.
[7]	Gordon RE, Nemeth JF, Singh S, et al., Harnessing SLE Autoantibodies for Intracellular Delivery of Biologic Therapeutics[J]. Trends Biotechnol,2021,39:298-310.
[8]	Stohl W, Schwarting A, Okada M, et al., Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus:A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study[J]. Arthritis Rheumatol,2017,69:1016-1027.
[9]	Steri M, Orru V, Idda ML, et al. Overexpression of the Cytokine BAFF and Autoimmunity Risk[J]. N Engl J Med,2017,376:1615-1626.
[10]	Raupov RK, Suspitsin EN, Imelbaev AI, et al. Simultaneous Onset of Pediatric Systemic Lupus Erythematosus in Twin Brothers:Case Report[J]. Front Pediatr,2022,10:929358.
[11]	Marion MC, Ramos PS, Bachali P, et al. Nucleic Acid-Sensing and Interferon-Inducible Pathways Show Differential Methylation in MZ Twins Discordant for Lupus and Overexpression in Independent Lupus Samples:Implications for Pathogenic Mechanism and Drug Targeting[J]. Genes (Basel), 2021, 12:1898.
[12]	Breitbach ME, Ramaker RC, Roberts K, et al. Population-Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus[J]. Arthritis Rheumatol,2020,72:282-291.
[13]	Hu N, Qiu X, Luo Y, et al. Abnormal histone modification patterns in lupus CD4+ T cells[J]. J Rheumatol,2008,35:804-810.
[14]	Gautam P, Sharma A, Bhatnagar A. Global histone modification analysis reveals hypoacetylated H3 and H4 histones in B Cells from systemic lupus erythematosus patients[J]. Immunol Lett, 2021,240:41-45.
[15]	Wardowska A, Komorniczak M, Bullo-Piontecka B, et al. Transcriptomic and Epigenetic Alterations in Dendritic Cells Correspond With Chronic Kidney Disease in Lupus Nephritis[J]. Front Immunol,2019,10:2026.
[16]	Pyfrom S, Paneru B, Knox JJ, et al. The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients[J]. Proc Natl Acad Sci U S A, 2021,118:e2024624118.
[17]	Zhang Q, Liang Y, Yuan H, et al. Integrated analysis of lncRNA, miRNA and mRNA expression profiling in patients with systemic lupus erythematosus[J]. Arch Med Sci,2019,15:872-879.
[18]	Alsheikh AJ, Wollenhaupt S, King EA, et al. The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases[J]. BMC Med Genomics, 2022,15:74.
[19]	Hiramatsu-Asano S, Wada J. Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus[J]. Acta Med Okayama, 2022,76:359-371.
[20]	Psarras A, Wittmann M, Vital EM. Emerging concepts of type I interferons in SLE pathogenesis and therapy[J]. Nat Rev Rheumatol, 2022,18:575-590.
[21]	Farkas L, Beiske K, Lund-Johansen F, et al. Plasmacytoid dendritic cells (natural interferonalpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions[J]. Am J Pathol, 2001,159:237-243.
[22]	Rowland SL, Riggs JM, Gilfillan S, et al. Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model[J]. J Exp Med, 2014, 211:1977-1991.
[23]	Klopp-Schulze L, Shaw JV, Dong JQ, et al. Applying Modeling and Simulations for Rational Dose Selection of Novel Toll-Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need[J]. Clin Pharmacol Ther,2022, 112:297-306.
[24]	Alunno A, Padjen I, Fanouriakis A, et al. Pathogenic and Therapeutic Relevance of JAK/STAT Signaling in Systemic Lupus Erythematosus:Integration of Distinct Inflammatory Pathways and the Prospect of Their Inhibition with an Oral Agent[J]. Cells, 2019, 8:898.
[25]	Furie RA, van Vollenhoven RF, Kalunian K, et al. Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus[J]. N Engl J Med, 2022, 387:894-904.
[26]	Kishimoto D, Kirino Y, Tamura M, et al. Dysregulated heme oxygenase-1(low) M2-like macrophages augment lupus nephritis via Bach1 induced by type I interferons[J]. Arthritis Res Ther, 2018, 20:64.
[27]	Willemsen L, de Winther MP. Macrophage subsets in atherosclerosis as defined by single-cell technologies[J]. J Pathol,2020, 250:705-714.
[28]	Ahamada MM, Jia Y, Wu X. Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus[J]. Front Immunol,2021, 12:734008.
[29]	Kucuksezer UC, Aktas Cetin E, Esen F, et al. The Role of Natural Killer Cells in Autoimmune Diseases[J]. Front Immunol, 2021, 12:622306.
[30]	Carmona-Rivera C, Kaplan MJ. Low-density granulocytes in systemic autoimmunity and autoinflammation[J]. Immunol Rev, 2022. doi: 10.1111/imr.13161.
[31]	Bolouri N, Akhtari M, Farhadi E, et al. Role of the innate and adaptive immune responses in the pathogenesis of systemic lupus erythematosus[J]. Inflamm Res,2022, 71:537-554.
[32]	Chen PM, Tsokos GC. T Cell Abnormalities in the Pathogenesis of Systemic Lupus Erythematosus:an Update[J]. Curr Rheumatol Rep, 2021, 23:12.
[33]	Furie RA, Bruce IN, Dorner T, et al. Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus[J]. Rheumatology (Oxford), 2021, 60:5397-5407.
[34]	Shan J, Jin H, Xu Y. T Cell Metabolism:A New Perspective on Th17/Treg Cell Imbalance in Systemic Lupus Erythematosus[J]. Front Immunol, 2020, 11:1027.
[35]	He J, Zhang R, Shao M, et al. Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus:a randomised, double-blind, placebo-controlled trial[J]. Ann Rheum Dis, 2020, 79:141-149.
[36]	Lai ZW, Kelly R, Winans T, et al. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications:a single-arm, open-label, phase 1/2 trial[J]. Lancet, 2018, 391:1186-1196.
[37]	Guillonneau C, Aubry V, Renaudin K, et al. Inhibition of chronic rejection and development of tolerogenic T cells after ICOS-ICOSL and CD40-CD40L co-stimulation blockade[J]. Transplantation,2005, 80:546-554.
[38]	Zhang J, Guo Q, Dai D, et al. Rapamycin-encapsulated costimulatory ICOS/CD40L-bispecific nanoparticles restrict pathogenic helper T-B-cell interactions while in situ suppressing mTOR for lupus treatment[J]. Biomaterials,2022, 289:121766.
[39]	Radziszewska A, Moulder Z, Jury EC, et al. CD8(+) T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease[J]. Int J Mol Sci, 2022, 23:11431.
[40]	Perez RK, Gordon MG, Subramaniam M, et al. Single-cell RNA-seq reveals cell type-specific molecular and genetic associations to lupus[J]. Science,2022, 376:eabf1970.
[41]	Lou H, Ling GS, Cao X. Autoantibodies in systemic lupus erythematosus:From immunopathology to therapeutic target[J]. J Autoimmun,2022,132:102861.
[42]	Jenks SA, Cashman KS, Zumaquero E, et al. Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus[J]. Immunity,2018, 49:725-739. e6.
[43]	Phalke S, Rivera-Correa J, Jenkins D, et al. Molecular mechanisms controlling age-associated B cells in autoimmunity[J]. Immunol Rev,2022, 307:79-100.
[44]	Matsushita T. Regulatory and effector B cells:Friends or foes?[J].J Dermatol Sci,2019, 93:2-7.
[45]	Mougiakakos D, Kronke G, Volkl S, et al. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus[J]. N Engl J Med,2021, 385:567-569.
[46]	Mackensen A, Muller F, Mougiakakos D, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus[J]. Nat Med, 2022, 28:2124-2132.
[47]	Zhang W, Feng J, Cinquina A, et al. Treatment of Systemic Lupus Erythematosus using BCMA-CD19 Compound CAR[J]. Stem Cell Rev Rep,2021,17:2120-2123.
[48]	Oh S, Mao X, Manfredo-Vieira S, et al. Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells[J]. Nat Biotechnol,2023. doi: 10.1038/s41587-022-01637-z.

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系统性红斑狼疮:从发病机制到新型靶向治疗

doi: 10.12290/xhyxzz.2022-0694

通讯作者:
吴小川,E-mail:xiaochuanwu@csu.edu.cn

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Systemic Lupus Erythematosus: From Pathogenesis to New Targeted Therapies

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系统性红斑狼疮:从发病机制到新型靶向治疗

doi: 10.12290/xhyxzz.2022-0694

通讯作者: 吴小川,E-mail:xiaochuanwu@csu.edu.cn

计量

出版历程

Systemic Lupus Erythematosus: From Pathogenesis to New Targeted Therapies

计量

出版历程

目录

通讯作者:
吴小川,E-mail:xiaochuanwu@csu.edu.cn