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Volume 14 Issue 2
Mar.  2023
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SHEN Tian, WU Xiaochuan. Systemic Lupus Erythematosus: from Pathogenesis to New Targeted Therapies[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(2): 234-240. DOI: 10.12290/xhyxzz.2022-0694
Citation: SHEN Tian, WU Xiaochuan. Systemic Lupus Erythematosus: from Pathogenesis to New Targeted Therapies[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(2): 234-240. DOI: 10.12290/xhyxzz.2022-0694
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Systemic Lupus Erythematosus: from Pathogenesis to New Targeted Therapies

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

Funds: 

National Key Research and Development Program of China 2021YFC2702004

National Natural Science Foundation of China Youth Project 82101905

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  • Corresponding author:

    WU Xiaochuan, E-mail: xiaochuanwu@csu.edu.cn

  • Received Date: December 04, 2022
  • Accepted Date: March 01, 2023
  • Available Online: March 11, 2023
  • Issue Publish Date: March 29, 2023
    Graphical Abstract
    • 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.
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    • References (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. DOI: 10.1038/s41467-021-21049-y
    [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. DOI: 10.1080/08923973.2021.1973493
    [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. DOI: 10.1038/s41584-021-00739-3
    [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. DOI: 10.1016/j.tibtech.2020.07.003
    [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. DOI: 10.1002/art.40049
    [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. DOI: 10.1056/NEJMoa1610528
    [10]
    Raupov RK, Suspitsin EN, Imelbaev AI, et al. Simul-taneous Onset of Pediatric Systemic Lupus Erythematosus in Twin Brothers: Case Report[J]. Front Pediatr, 2022, 10: 929358. DOI: 10.3389/fped.2022.929358
    [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. DOI: 10.3390/genes12121898
    [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. DOI: 10.1002/art.41083
    [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. DOI: 10.1016/j.imlet.2021.09.007
    [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. DOI: 10.3389/fimmu.2019.02026
    [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. DOI: 10.1073/pnas.2024624118
    [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. DOI: 10.5114/aoms.2018.79145
    [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. DOI: 10.1186/s12920-022-01216-w
    [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 interferon-alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions[J]. Am J Pathol, 2001, 159: 237-243. DOI: 10.1016/S0002-9440(10)61689-6
    [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. DOI: 10.1084/jem.20132620
    [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. DOI: 10.1002/cpt.2606
    [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. DOI: 10.3390/cells8080898
    [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. DOI: 10.1056/NEJMoa2118025
    [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. DOI: 10.1186/s13075-018-1568-1
    [27]
    Willemsen L, de Winther MP. Macrophage subsets in atherosclerosis as defined by single-cell technologies[J]. J Pathol, 2020, 250: 705-714. DOI: 10.1002/path.5392
    [28]
    Ahamada MM, Jia Y, Wu X. Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus[J]. Front Immunol, 2021, 12: 734008. DOI: 10.3389/fimmu.2021.734008
    [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. DOI: 10.3389/fimmu.2021.622306
    [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. DOI: 10.1007/s00011-022-01554-6
    [32]
    Chen PM, Tsokos GC. T Cell Abnormalities in the Pathogenesis of Systemic Lupus Erythematosus: an Update[J]. Curr Rheumatol Rep, 2021, 23: 12. DOI: 10.1007/s11926-020-00978-5
    [33]
    Furie RA, Bruce IN, Dorner T, et al. Phase 2, rando-mized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus[J]. Rheumatology (Oxford), 2021, 60: 5397-5407. DOI: 10.1093/rheumatology/keab381
    [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. DOI: 10.3389/fimmu.2020.01027
    [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. DOI: 10.1016/S0140-6736(18)30485-9
    [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. DOI: 10.1016/j.biomaterials.2022.121766
    [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. DOI: 10.3390/ijms231911431
    [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. DOI: 10.1126/science.abf1970
    [41]
    Lou H, Ling GS, Cao X. Autoantibodies in systemic lupus erythematosus: From immunopathology to therapeutic target[J]. J Autoimmun, 2022, 132: 102861. DOI: 10.1016/j.jaut.2022.102861
    [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. DOI: 10.1016/j.immuni.2018.08.015
    [43]
    Phalke S, Rivera-Correa J, Jenkins D, et al. Molecular mechanisms controlling age-associated B cells in autoim-munity[J]. Immunol Rev, 2022, 307: 79-100. DOI: 10.1111/imr.13068
    [44]
    Matsushita T. Regulatory and effector B cells: Friends or foes?[J]. J Dermatol Sci, 2019, 93: 2-7. DOI: 10.1016/j.jdermsci.2018.11.008
    [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. DOI: 10.1056/NEJMc2107725
    [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. DOI: 10.1038/s41591-022-02017-5
    [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. DOI: 10.1007/s12015-021-10251-6
    [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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