New Mechanisms and Therapeutic Targets in Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a multifaceted dautoimmune disease driven by complex interactions among genetic, environmental, and sex-related factors. Central to its pathogenesis are type I interferons (IFN-I) and autoantibodies that target nucleic acids and nucleic acid-binding proteins. These mediators, often triggered by environmental stimuli in genetically susceptible individuals, promote sustained immune activation and chronic inflammation. Despite advances in understanding the immunological landscape of SLE, the precise initiating triggers and early molecular events remain incompletely defined. Recent studies have highlighted the destabilization of innate immune cells, particularly dendritic cells and monocytes, as critical early events in the pathogenesis of SLE. These alterations precede and potentially initiate the downstream activation of autoreactive lymphocytes. This review provides an updated synthesis of key epidemiological findings, emerging pathogenic mechanisms, potential therapeutic targets, and advances in translational and clinical research. Particular attention is given to recent insights into disease triggers and early pathological processes, especially the destabilization of innate immune cells. By consolidating these advances, this review aims to refine our understanding of the early immune dysregulation in SLE and to support the development of more precise, mechanism-based therapeutic strategies.

Keywords

epidemiology / mechanism / systemic lupus erythematosus / therapeutic targets / type I interferon

References

[1] G. J. Pons-Estel, G. S. Alarcón, L. Scofield, L. Reinlib, and G. S. Cooper, “Understanding the Epidemiology and Progression of Systemic Lupus Erythematosus,” Seminars in Arthritis and Rheumatism 39, no. 4 (2010): 257-268.

[2] J. Tian, D. Zhang, X. Yao, Y. Huang, and Q. Lu, “Global Epidemiology of Systemic Lupus Erythematosus: A Comprehensive Systematic Analysis and Modelling Study,” Annals of the Rheumatic Diseases 82, no. 3 (2023): 351-356.

[3] M. R. W. Barber, C. Drenkard, T. Falasinnu, et al., “Global Epidemiology of Systemic Lupus Erythematosus,” Nature Reviews Rheumatology 17, no. 9 (2021): 515-532.

[4] F. Fatoye, T. Gebrye, and C. Mbada, “Global and Regional Prevalence and Incidence of Systemic Lupus Erythematosus in Low-and-middle Income Countries: A Systematic Review and Meta-analysis,” Rheumatology International 42, no. 12 (2022): 2097-2107.

[5] M. Zen, L. Salmaso, C. Barbiellini Amidei, et al., “Mortality and Causes of Death in Systemic Lupus Erythematosus Over the Last Decade: Data From a Large Population-based Study,” European Journal of Internal Medicine 112 (2023): 45-51.

[6] M. Dall'Era, M. G. Cisternas, K. Snipes, L. J. Herrinton, C. Gordon, and C. G. Helmick, “The Incidence and Prevalence of Systemic Lupus Erythematosus in San Francisco County, California: The California Lupus Surveillance Project,” Arthritis & Rheumatology 2017; 69(10): 1996-2005.

[7] P. M. Izmirly, I. Wan, S. Sahl, et al., “The Incidence and Prevalence of Systemic Lupus Erythematosus in New York County (Manhattan), New York: The Manhattan Lupus Surveillance Program,” Arthritis & Rheumatology 69, no. 10 (2017): 2006-2017.

[8] P. M. Izmirly, E. D. Ferucci, E. C. Somers, et al., “Incidence Rates of Systemic Lupus Erythematosus in the USA: Estimates From a Meta-analysis of the Centers for Disease Control and Prevention National Lupus Registries,” Lupus Science & Medicine 8, no. 1 (2021): e000614.

[9] P. M. Izmirly, H. Parton, L. Wang, et al., “Prevalence of Systemic Lupus Erythematosus in the United States: Estimates From a Meta-analysis of the Centers for Disease Control and Prevention National Lupus Registries,” Arthritis & Rheumatology 73, no. 6 (2021): 991-996.

[10] F. Rees, M. Doherty, M. Grainge, G. Davenport, P. Lanyon, and W. Zhang, “The Incidence and Prevalence of Systemic Lupus Erythematosus in the UK, 1999-2012,” Annals of the Rheumatic Diseases 75, no. 1 (2016): 136-141.

[11] E. C. Somers, W. Marder, P. Cagnoli, et al., “Population-based Incidence and Prevalence of Systemic Lupus Erythematosus: The Michigan Lupus Epidemiology and Surveillance program,” Arthritis & Rheumatology 66, no. 2 (2014): 369-378.

[12] R. W. Jakes, S. Bae, W. Louthrenoo, C. Mok, S. V. Navarra, and N. Kwon, “Systematic Review of the Epidemiology of Systemic Lupus Erythematosus in the Asia-Pacific region: Prevalence, Incidence, Clinical Features, and Mortality,” Arthritis Care & Research (Hoboken) 64, no. 2 (2012): 159-168.

[13] O. N. Pamuk, A. A. Raza, and S. Hasni, “Neuropsychiatric Lupus in Late- and Early-onset Systemic Lupus Erythematosus Patients: A Systematic Review and Meta-analysis,” Rheumatology 63, no. 1 (2024): 8-15.

[14] M. K. Crow, “Pathogenesis of Systemic Lupus Erythematosus: Risks, Mechanisms and Therapeutic Targets,” Annals of the Rheumatic Diseases 82, no. 8 (2023): 999-1014.

[15] R. A. Furie, R. F. Van Vollenhoven, K. Kalunian, et al., “Trial of Anti-BDCA2 Antibody litifilimab for Systemic Lupus Erythematosus,” New England Journal of Medicine 387, no. 10 (2022): 894-904.

[16] R. Furie, B. H. Rovin, F. Houssiau, et al., “Two-year, Randomized, Controlled Trial of belimumab in Lupus Nephritis,” New England Journal of Medicine 383, no. 12 (2020): 1117-1128.

[17] S. V. Navarra, R. M. Guzmán, A. E. Gallacher, et al., “Efficacy and Safety of belimumab in Patients With Active Systemic Lupus Erythematosus: A Randomised, Placebo-controlled, Phase 3 Trial,” Lancet 377, no. 9767 (2011): 721-731.

[18] R. A. Eisenberg, S. Y. Craven, R. W. Warren, and P. L. Cohen, “Stochastic Control of Anti-Sm Autoantibodies in MRL/Mp-lpr/Lpr Mice,” Journal of Clinical Investigation 80, no. 3 (1987): 691-697.

[19] Y. Deng and B. P. Tsao, “Genetic Susceptibility to Systemic Lupus Erythematosus in the Genomic Era,” Nature Reviews Rheumatology 6, no. 12 (2010): 683-692.

[20] M. Koga, A. Kawasaki, I. Ito, et al., “Cumulative Association of Eight Susceptibility Genes With Systemic Lupus Erythematosus in a Japanese Female Population,” Journal of Human Genetics 56, no. 7 (2011): 503-507.

[21] C. Wang, A. Ahlford, T. M. Järvinen, et al., “Genes Identified in Asian SLE GWASs Are Also Associated With SLE in Caucasian Populations,” European Journal of Human Genetics 21, no. 9 (2013): 994-999.

[22] D. Deafen, A. Escalante, L. Weinrib, et al., “A Revised Estimate of Twin Concordance in Systemic Lupus erythematosus,” Arthritis and Rheumatism 35, no. 3 (1992): 311-318.

[23] C. F. Kuo, M. J. Grainge, A. M. Valdes, et al., “Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families,” JAMA Internal Medicine 175, no. 9 (2015): 1518.

[24] D. Alarcón-Segovia, M. E. Alarcón-Riquelme, M. H. Cardiel, et al., “Familial Aggregation of Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Other Autoimmune Diseases in 1,177 Lupus Patients From the GLADEL Cohort,” Arthritis and Rheumatism 52, no. 4 (2005): 1138-1147.

[25] X. Yin, K. Kim, H. Suetsugu, et al., “Biological Insights Into Systemic Lupus Erythematosus Through an Immune Cell-specific Transcriptome-wide Association Study,” Annals of the Rheumatic Diseases 81, no. 9 (2022): 1273-1280.

[26] M. E. Alarcón-Riquelme, J. T. Ziegler, J. Molineros, et al., “Genome-wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture,” Arthritis & Rheumatology 68, no. 4 (2016): 932-943.

[27] The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), J. B. Harley, M. E. Alarcón-Riquelme, et al., The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), “Genome-wide Association Scan in Women With Systemic Lupus Erythematosus Identifies Susceptibility Variants in ITGAM, PXK, KIAA1542 and Other Loci,” Nature Genetics 40, no. 2 (2008): 204-210.

[28] D. L. Armstrong, R. Zidovetzki, M. E. Alarcón-Riquelme, et al., “GWAS Identifies Novel SLE Susceptibility Genes and Explains the Association of the HLA Region,” Genes and Immunity 15, no. 6 (2014): 347-354.

[29] P. Raj, E. Rai, R. Song, et al., “Regulatory Polymorphisms Modulate the Expression of HLA Class II Molecules and Promote Autoimmunity,” Elife 5 (2016): e12089.

[30] Y. F. Wang, Y. Zhang, Z. Lin, et al., “Identification of 38 Novel Loci for Systemic Lupus Erythematosus and Genetic Heterogeneity Between Ancestral Groups,” Nature Communications 12, no. 1 (2021): 772.

[31] J. E. Salmon, S. Millard, L. A. Schachter, et al., “Fc Gamma RIIA Alleles Are Heritable Risk Factors for Lupus Nephritis in African Americans,” Journal of Clinical Investigation 97, no. 5 (1996): 1348-1354.

[32] S. A. Jones, S. Cantsilieris, H. Fan, et al., “Rare Variants in Non-coding Regulatory Regions of the Genome That Affect Gene Expression in Systemic Lupus Erythematosus,” Scientific Reports 9, no. 1 (2019): 15433.

[33] C. D. Langefeld, H. C. Ainsworth, D. S. C. Graham, et al., “Transancestral Mapping and Genetic Load in Systemic Lupus erythematosus,” Nature Communications 8, no. 1 (2017): 16021.

[34] N. K. W. Yeo, C. K. Lim, K. N. Yaung, et al., “Genetic Interrogation for Sequence and Copy Number Variants in Systemic Lupus Erythematosus,” Frontiers in Genetics 15 (2024): 1341272.

[35] A. Kaul, C. Gordon, M. K. Crow, et al., “Systemic lupus erythematosus,” Nature Reviews Disease Primers 2, no. 1 (2016): 16039.

[36] D. R. Dou, Y. Zhao, J. A. Belk, et al., “Xist Ribonucleoproteins Promote Female Sex-biased Autoimmunity,” Cell 187, no. 3 (2024): 733-749. e16.

[37] W. A. James, E. Ogunrinde, Z. Wan, et al., “A Distinct Plasma Microbiome but Not Gut Microbiome in Patients With Systemic Lupus Erythematosus Compared to Healthy Individuals,” Journal of Rheumatology 49, no. 6 (2022): 592-597.

[38] F. Liu, T. Ren, X. Li, et al., “Distinct Microbiomes of Gut and Saliva in Patients With Systemic Lupus Erythematous and Clinical Associations,” Frontiers in Immunology 12 (2021): 626217.

[39] A. Hevia, C. Milani, P. López, et al., “Intestinal Dysbiosis Associated With Systemic Lupus Erythematosus. Segata N, Bello MGD, Eds,” MBio 5, no. 5 (2014). e01548-14.

[40] Q. Xu, J. J. Ni, B. X. Han, et al., “Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-sample Mendelian Randomization Study,” Frontiers in immunology 12 (2022): 746998.

[41] B. Z. Li, H. Wang, X. B. Li, et al., “Altered Gut Fungi in Systemic Lupus Erythematosus - A Pilot Study,” Frontiers in Microbiology 13 (2022): 1031079.

[42] Y. F. Chen, A. H. Hsieh, L. C. Wang, et al., “Fecal Microbiota Changes in NZB/W F1 Mice After Induction of Lupus Disease,” Scientific Reports 11, no. 1 (2021): 22953.

[43] D. F. Zegarra-Ruiz, A. El Beidaq, A. J. Iñiguez, et al., “A Diet-sensitive Commensal lactobacillus Strain Mediates TLR7-dependent Systemic Autoimmunity,” Cell Host & Microbe 25, no. 1 (2019): 113-127. e6.

[44] S. Saithong, W. Saisorn, P. Visitchanakun, K. Sae-khow, D. Chiewchengchol, and A. Leelahavanichkul, “A Synergy Between Endotoxin and (1→3)-beta-D-glucan Enhanced Neutrophil Extracellular Traps in candida Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- lupus Mice, an Impact of Intestinal Fungi in Lupus,” Journal of Inflammation Research 14 (2021): 2333-2352.

[45] S. Manfredo Vieira, M. Hiltensperger, V. Kumar, et al., “Translocation of a Gut Pathobiont Drives Autoimmunity in Mice and Humans,” Science 359, no. 6380 (2018): 1156-1161.

[46] T. M. Greiling, C. Dehner, X. Chen, et al., “Commensal Orthologs of the human Autoantigen Ro60 as Triggers of Autoimmunity in Lupus,” Science Translational Medicine 10, no. 434 (2018): eaan2306.

[47] B. Chen, X. Jia, J. Xu, et al., “An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus,” Arthritis & Rheumatology 73, no. 2 (2021): 232-243.

[48] M. Shirakashi, M. Maruya, K. Hirota, et al., “Effect of Impaired T Cell Receptor Signaling on the Gut Microbiota in a Mouse Model of Systemic Autoimmunity,” Arthritis & Rheumatology 74, no. 4 (2022): 641-653.

[49] M. Zouali, “B Lymphocytes, the Gastrointestinal Tract and Autoimmunity,” Autoimmunity Reviews 20, no. 4 (2021): 102777.

[50] C. L. P. Thio, P. Y. Chi, A. C. Y. Lai, and Y. J. Chang, “Regulation of Type 2 Innate Lymphoid Cell-dependent Airway Hyperreactivity by Butyrate,” Journal of Allergy and Clinical Immunology 142, no. 6 (2018): 1867-1883. e12.

[51] H. N. Sanchez, J. B. Moroney, H. Gan, et al., “B Cell-intrinsic Epigenetic Modulation of Antibody Responses by Dietary fiber-derived Short-chain Fatty Acids,” Nature Communications 11, no. 1 (2020): 60.

[52] Y. Liu, Y. Hou, G. Wang, X. Zheng, and H. Hao, “Gut Microbial Metabolites of Aromatic Amino Acids as Signals in Host-microbe Interplay,” Trends in Endocrinology and Metabolism 31, no. 11 (2020): 818-834.

[53] S. C. Choi, J. Brown, M. Gong, et al., “Gut Microbiota Dysbiosis and Altered Tryptophan Catabolism Contribute to Autoimmunity in Lupus-susceptible Mice,” Science Translational Medicine 12, no. 551 (2020): eaax2220.

[54] H. Hong, F. Alduraibi, D. Ponder, et al., “Host Genetics but Not Commensal Microbiota Determines the Initial Development of Systemic Autoimmune Disease in BXD2 Mice,” Arthritis & Rheumatology 74, no. 4 (2022): 634-640.

[55] R. M. Clancy, M. C. Marion, H. C. Ainsworth, et al., “Gut Dysbiosis and the Clinical Spectrum in anti-Ro Positive Mothers of Children With Neonatal Lupus,” Gut Microbes 14, no. 1 (2022): 2081474.

[56] T. Kobayashi, S. Naik, and K. Nagao, “Choreographing Immunity in the Skin Epithelial Barrier,” Immunity 50, no. 3 (2019): 552-565.

[57] M. Pasparakis, I. Haase, and F. O. Nestle, “Mechanisms Regulating Skin Immunity and Inflammation,” Nature Reviews Immunology 14, no. 5 (2014): 289-301.

[58] J. H. Epstein, D. Tuffanelli, and E. L. Dubois, “Light Sensitivity and Lupus Erythematosus,” Archives of Dermatology 91 (1965): 483-485.

[59] C. J. G. Sanders, H. Van Weelden, G. A. A. Kazzaz, V. Sigurdsson, J. Toonstra, and C. Bruijnzeel-Koomen, “Photosensitivity in Patients With Lupus erythematosus: A Clinical and Photobiological Study of 100 Patients Using a Prolonged Phototest Protocol,” British Journal of Dermatology 149, no. 1 (2003): 131-137.

[60] F. O. Nestle, P. Di Meglio, J. Z. Qin, and B. J. Nickoloff, “Skin Immune Sentinels in Health and Disease,” Nature Reviews Immunology 9, no. 10 (2009): 679-691.

[61] L. C. Tsoi, G. A. Hile, C. C. Berthier, et al., “Hypersensitive IFN Responses in Lupus Keratinocytes Reveal Key Mechanistic Determinants in Cutaneous Lupus,” Journal of Immunology 202, no. 7 (2019): 2121-2130.

[62] M. Martin-Fernandez, M. Bravo García-Morato, C. Gruber, et al., “Systemic Type I IFN Inflammation in human ISG15 Deficiency Leads to Necrotizing Skin Lesions,” Cell Reports 31, no. 6 (2020): 107633.

[63] L. J. Zhang, G. L. Sen, N. L. Ward, et al., “Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes During Skin Injury,” Immunity 45, no. 1 (2016): 119-130.

[64] H. Shirota, K. J. Ishii, H. Takakuwa, and D. M. Klinman, “Contribution of Interferon-beta to the Immune Activation Induced by Double-stranded DNA,” Immunology 118, no. 3 (2006): 302-310.

[65] A. Decout, J. D. Katz, S. Venkatraman, and A. Ablasser, “The cGAS-STING Pathway as a Therapeutic Target in Inflammatory Diseases,” Nature Reviews Immunology 21, no. 9 (2021): 548-569.

[66] J. Tian, D. Zhang, V. Kurbatov, et al., “5-fluorouracil Efficacy Requires Anti-tumor Immunity Triggered by Cancer-cell-intrinsic STING,” Embo Journal 40, no. 7 (2021): e106065.

[67] E. Der, H. Suryawanshi, P. Morozov, et al., “Tubular Cell and Keratinocyte Single-cell Transcriptomics Applied to Lupus Nephritis Reveal Type I IFN and Fibrosis Relevant Pathways,” Nature Immunology 20, no. 7 (2019): 915-927.

[68] S. Caielli, Z. Wan, and V. Pascual, “Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond,” Annual Review of Immunology 41 (2023): 533-560.

[69] A. Psarras, A. Alase, A. Antanaviciute, et al., “Functionally Impaired Plasmacytoid Dendritic Cells and Non-haematopoietic Sources of Type I Interferon Characterize human Autoimmunity,” Nature Communications 11, no. 1 (2020): 6149.

[70] A. Psarras, M. Wittmann, and E. M. Vital, “Emerging Concepts of Type I Interferons in SLE Pathogenesis and Therapy,” Nature Reviews Rheumatology 18, no. 10 (2022): 575-590.

[71] S. Skopelja-Gardner, J. Tai, X. Sun, et al., “Acute Skin Exposure to Ultraviolet Light Triggers Neutrophil-mediated Kidney Inflammation,” PNAS 118, no. 3 (2021): e2019097118.

[72] E. Der, S. Ranabothu, H. Suryawanshi, et al., “Single Cell RNA Sequencing to Dissect the Molecular Heterogeneity in Lupus Nephritis,” JCI Insight 2, no. 9 (2017): e93009.

[73] M. K. Crow, M. Olferiev, and K. A. Kirou, “Targeting of Type I Interferon in Systemic Autoimmune Diseases,” Translational Research 165, no. 2 (2015): 296-305.

[74] G. S. Garcia-Romo, S. Caielli, B. Vega, et al., “Netting Neutrophils Are Major Inducers of Type I IFN Production in Pediatric Systemic Lupus Erythematosus,” Science Translational Medicine 3, no. 73 (2011): 73ra20.

[75] Y. He, F. Y. Yang, and E. W. Sun, “Neutrophil Extracellular Traps in Autoimmune Diseases,” Chinese Medical Journal 131, no. 13 (2018): 1513-1519.

[76] E. Frangou, A. Chrysanthopoulou, A. Mitsios, et al., “REDD1/autophagy Pathway Promotes Thromboinflammation and Fibrosis in human Systemic Lupus Erythematosus (SLE) Through NETs Decorated With Tissue Factor (TF) and Interleukin-17A (IL-17A),” Annals of the Rheumatic Diseases 78, no. 2 (2019): 238-248.

[77] M. Malamud, L. Whitehead, A. McIntosh, et al., “Recognition and Control of Neutrophil Extracellular Trap Formation by MICL,” Nature 633, no. 8029 (2024): 442-450.

[78] J. Shen, F. Li, X. Han, et al., “Gasdermin D Deficiency Aborts Myeloid Calcium Influx to Drive Granulopoiesis in Lupus Nephritis,” Cell Communication and Signaling 22, no. 1 (2024): 308.

[79] N. Miao, Z. Wang, Q. Wang, et al., “Oxidized Mitochondrial DNA Induces Gasdermin D Oligomerization in Systemic Lupus Erythematosus,” Nature Communications 14, no. 1 (2023): 872.

[80] X. Jiang, X. Xiao, H. Li, et al., “Oxidized Galectin-1 in SLE Fails to Bind the Inhibitory Receptor VSTM1 and Increases Reactive Oxygen Species Levels in Neutrophils,” Cellular & Molecular Immunology 20, no. 11 (2023): 1339-1351.

[81] I. Puga, M. Cols, C. M. Barra, et al., “B Cell-helper Neutrophils Stimulate the Diversification and Production of Immunoglobulin in the Marginal Zone of the Spleen,” Nature Immunology 13, no. 2 (2012): 170-180.

[82] R. Banchereau, S. Hong, B. Cantarel, et al., “Personalized Immunomonitoring Uncovers Molecular Networks That Stratify lupus Patients,” Cell 165, no. 3 (2016): 551-565.

[83] A. A. Bengtsson, Å. Pettersson, S. Wichert, et al., “Low Production of Reactive Oxygen Species in Granulocytes Is Associated With Organ Damage in Systemic Lupus Erythematosus,” Arthritis Research & Therapy 16, no. 3 (2014): R120.

[84] P. Linge, S. Arve, L. M. Olsson, et al., “NCF1-339 polymorphism Is Associated With Altered Formation of Neutrophil Extracellular Traps, High Serum Interferon Activity and Antiphospholipid Syndrome in Systemic Lupus Erythematosus,” Annals of the Rheumatic Diseases 79, no. 2 (2020): 254-261.

[85] L. M. Olsson, Å. C. Johansson, B. Gullstrand, et al., “A Single Nucleotide Polymorphism in the NCF1 Gene Leading to Reduced Oxidative Burst Is Associated With Systemic Lupus Erythematosus,” Annals of the Rheumatic Diseases 76, no. 9 (2017): 1607-1613.

[86] J. Zhao, J. Ma, Y. Deng, et al., “A Missense Variant in NCF1 Is Associated With Susceptibility to Multiple Autoimmune Diseases,” Nature Genetics 49, no. 3 (2017): 433-437.

[87] P. Li, M. Jiang, K. Li, et al., “Glutathione Peroxidase 4-regulated Neutrophil Ferroptosis Induces Systemic Autoimmunity,” Nature Immunology 22, no. 9 (2021): 1107-1117.

[88] H. Terui, K. Yamasaki, M. Wada-Irimada, et al., “Staphylococcus aureus Skin Colonization Promotes SLE-Like Autoimmune Inflammation via Neutrophil Activation and the IL-23/IL-17 Axis,” Science Immunology 7, no. 76 (2022): eabm9811.

[89] G. Sule, B. H. Abuaita, P. A. Steffes, et al., “Endoplasmic Reticulum Stress Sensor IRE1α Propels Neutrophil Hyperactivity in Lupus,” Journal of Clinical Investigation 131, no. 7 (2021): e137866.

[90] T. Lövgren, M. Eloranta, U. Båve, G. V. Alm, and L. Rönnblom, “Induction of Interferon-α Production in Plasmacytoid Dendritic Cells by Immune Complexes Containing Nucleic Acid Released by Necrotic or Late Apoptotic Cells and Lupus IgG,” Arthritis and Rheumatism 50, no. 6 (2004): 1861-1872.

[91] F. J. Barrat, T. Meeker, J. Gregorio, et al., “Nucleic Acids of Mammalian Origin Can Act as Endogenous Ligands for Toll-Like Receptors and May Promote Systemic Lupus Erythematosus,” Journal of Experimental Medicine 202, no. 8 (2005): 1131-1139.

[92] S. Karrar and D. S. Cunninghame Graham, “Review: Abnormal B Cell Development in Systemic Lupus erythematosus: What the Genetics Tell Us,” Arthritis & Rheumatology 70, no. 4 (2018): 496-507.

[93] Y. Meng, J. Ma, C. Yao, et al., “The NCF1 Variant p.R90H Aggravates Autoimmunity by Facilitating the Activation of Plasmacytoid Dendritic Cells,” Journal of Clinical Investigation 132, no. 16 (2022): e153619.

[94] S. L. Rowland, J. M. Riggs, S. Gilfillan, et al., “Early, Transient Depletion of Plasmacytoid Dendritic Cells Ameliorates Autoimmunity in a lupus Model,” Journal of Experimental Medicine 211, no. 10 (2014): 1977-1991.

[95] J. M. Kim, S. H. Park, H. Y. Kim, and S. K. Kwok, “A Plasmacytoid Dendritic Cells-type I Interferon Axis Is Critically Implicated in the Pathogenesis of Systemic Lupus Erythematosus,” International Journal of Molecular Sciences 16, no. 6 (2015): 14158-14170.

[96] C. Guiducci, M. Gong, Z. Xu, et al., “TLR Recognition of Self Nucleic Acids Hampers Glucocorticoid Activity in Lupus,” Nature 465, no. 7300 (2010): 937-941.

[97] K. M. Grzes, D. E. Sanin, A. M. Kabat, et al., “Plasmacytoid Dendritic Cell Activation Is Dependent on Coordinated Expression of Distinct Amino Acid Transporters,” Immunity 54, no. 11 (2021): 2514-2530. e7.

[98] P. Blanco, A. K. Palucka, M. Gill, V. Pascual, and J. Banchereau, “Induction of Dendritic Cell Differentiation by IFN-α in Systemic Lupus Erythematosus,” Science 294, no. 5546 (2001): 1540-1543.

[99] V. F. Ntasis, N. I. Panousis, M. G. Tektonidou, et al., “Extensive Fragmentation and Re-organization of Transcription in Systemic Lupus erythematosus,” Scientific Reports 10, no. 1 (2020): 16648.

[100] E. Corsiero, A. Nerviani, M. Bombardieri, and C. Pitzalis, “Ectopic Lymphoid Structures: Powerhouse of Autoimmunity,” Frontiers in Immunology 7 (2016): 430.

[101] C. Jacquemin, N. Schmitt, C. Contin-Bordes, et al., “OX40 ligand Contributes to human Lupus Pathogenesis by Promoting T Follicular Helper Response,” Immunity 42, no. 6 (2015): 1159-1170.

[102] W. Chen, B. Jin, C. Cheng, et al., “Single-cell Profiling Reveals Kidney CD163+ Dendritic Cell Participation in human Lupus Nephritis,” Annals of the Rheumatic Diseases 83, no. 5 (2024): 608-623.

[103] J. Tian, L. Shi, D. Zhang, et al., “Dysregulation in Keratinocytes Drives Systemic Lupus Erythematosus Onset,” Cellular & Molecular Immunology 22, no. 1 (2024): 83-96.

[104] N. Bolouri, M. Akhtari, E. Farhadi, et al., “Role of the Innate and Adaptive Immune Responses in the Pathogenesis of Systemic Lupus Erythematosus,” Inflammation Research 71, no. 5-6 (2022): 537-554.

[105] C. Huret, L. Ferrayé, A. David, et al., “Altered X-chromosome Inactivation Predisposes to Autoimmunity,” Science Advances 10, no. 18 (2024): eadn6537.

[106] H. Wang, M. Shen, Y. Ma, et al., “Novel Mitophagy Inducer Alleviates Lupus Nephritis by Reducing Myeloid Cell Activation and Autoantigen Presentation,” Kidney International 105, no. 4 (2024): 759-774.

[107] M. Zheng, Z. Hu, X. Mei, et al., “Single-cell Sequencing Shows Cellular Heterogeneity of Cutaneous Lesions in lupus erythematosus,” Nature Communications 13, no. 1 (2022): 7489.

[108] V. Umare, V. Pradhan, M. Nadkar, et al., “Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients,” Mediators of Inflammation 2014 (2014): 1-8.

[109] Z. G. Ramirez-Ortiz, A. Prasad, J. W. Griffith, et al., “The Receptor TREML4 Amplifies TLR7-mediated Signaling During Antiviral Responses and Autoimmunity,” Nature Immunology 16, no. 5 (2015): 495-504.

[110] C. Wolf, E. L. Lim, M. Mokhtari, et al., “UNC93B1 variants Underlie TLR7-dependent Autoimmunity,” Science Immunology 9, no. 92 (2024): eadi9769.

[111] A. G. Ferreté-Bonastre, M. Martínez-Gallo, O. Morante-Palacios, et al., “Disease Activity Drives Divergent Epigenetic and Transcriptomic Reprogramming of Monocyte Subpopulations in Systemic Lupus Erythematosus,” Annals of the Rheumatic Diseases 83, no. 7 (2024): 1-14.

[112] S. Caielli, P. Balasubramanian, J. Rodriguez-Alcazar, et al., “Type I IFN Drives Unconventional IL-1β Secretion in Lupus Monocytes,” Immunity 57, no. 11 (2024): 2497-2513. e12.

[113] N. I. Panousis, G. K. Bertsias, H. Ongen, et al., “Combined Genetic and Transcriptome Analysis of Patients With SLE: Distinct, Targetable Signatures for Susceptibility and Severity,” Annals of the Rheumatic Diseases 78, no. 8 (2019): 1079-1089.

[114] the Accelerating Medicines Partnership in SLE network, A. Arazi, D. A. Rao, et al., the Accelerating Medicines Partnership in SLE network, “The Immune Cell Landscape in Kidneys of Patients With Lupus Nephritis,” Nature Immunology 20, no. 7 (2019): 902-914.

[115] Y. Xin, C. Gao, L. Wang, Q. Liu, and Q. Lu, “Lipopolysaccharide Released From Gut Activates Pyroptosis of Macrophages via Caspase 11-gasdermin D Pathway in Systemic Lupus Erythematosus,” MedComm 5, no. 6 (2024): e610.

[116] E. J. Yoo, K. H. Oh, H. Piao, et al., “Macrophage Transcription Factor TonEBP Promotes Systemic Lupus Erythematosus and Kidney Injury via Damage-induced Signaling Pathways,” Kidney International 104, no. 1 (2023): 163-180.

[117] S. Caielli, J. Cardenas, A. A. De Jesus, et al., “Erythroid Mitochondrial Retention Triggers Myeloid-dependent Type I Interferon in human SLE,” Cell 184, no. 17 (2021): 4464-4479. e19.

[118] B. Hervier, V. Beziat, J. Haroche, et al., “Phenotype and Function of Natural Killer Cells in Systemic Lupus Erythematosus: Excess Interferon-γ Production in Patients With Active Disease,” Arthritis and Rheumatism 63, no. 6 (2011): 1698-1706.

[119] D. Schepis, I. Gunnarsson, M. Eloranta, et al., “Increased Proportion of CD56bright Natural Killer Cells in Active and Inactive Systemic Lupus Erythematosus,” Immunology 126, no. 1 (2009): 140-146.

[120] A. Henriques, L. Teixeira, L. Inês, et al., “NK Cells Dysfunction in Systemic lupus erythematosus: Relation to Disease Activity,” Clinical Rheumatology 32, no. 6 (2013): 805-813.

[121] J. Tchen, Q. Simon, L. Chapart, et al., “CT-M8 Mice: A New Mouse Model Demonstrates That Basophils Have a Nonredundant Role in Lupus-Like Disease Development,” Frontiers in Immunology 13 (2022): 900532.

[122] M. Halfon, D. Bachelet, G. Hanouna, et al., “CD62L on Blood Basophils: A First Pre-treatment Predictor of Remission in Severe Lupus Nephritis,” Nephrology, Dialysis, Transplantation 36, no. 12 (2021): 2256-2262.

[123] Y. Jiang, J. Chen, Y. Zhao, Y. Liu, H. Xu, and X. Mo, “Basophils as a Potential Marker of Lupus Nephritis by Flow Cytometry,” Future Science OA 7, no. 5 (2021): FSO690.

[124] C. Pellefigues and N. Charles, “The Deleterious Role of Basophils in Systemic Lupus Erythematosus,” Current Opinion in Immunology 25, no. 6 (2013): 704-711.

[125] J. Tchen, Q. Simon, L. Chapart, et al., “PD-L1- and IL-4-expressing Basophils Promote Pathogenic Accumulation of T Follicular Helper Cells in Lupus,” Nature Communications 15, no. 1 (2024): 3389.

[126] C. Huang, F. Li, J. Wang, and Z. Tian, “Innate-Like Lymphocytes and Innate Lymphoid Cells in Asthma,” Clinical Reviews in Allergy & Immunology 59, no. 3 (2020): 359-370.

[127] C. Guo, M. Zhou, S. Zhao, et al., “Innate Lymphoid Cell Disturbance With Increase in ILC1 in Systemic Lupus Erythematosus,” Clinical Immunology 202 (2019): 49-58.

[128] M. Hou and S. Liu, “Innate Lymphoid Cells Are Increased in Systemic Lupus Erythematosus,” Clinical and Experimental Rheumatology 37, no. 4 (2019): 676-679.

[129] S. I. Biniaris-Georgallis, T. Aschman, K. Stergioula, et al., “Amplification of Autoimmune Organ Damage by NKp46-activated ILC1s,” Nature 634, no. 8035 (2024): 952-960.

[130] C. Cassius, M. Branchtein, M. Battistella, et al., “Persistent Deficiency of Mucosal-associated Invariant T Cells During Dermatomyositis,” Rheumatology 59, no. 9 (2020): 2282-2286.

[131] E. Litvinova, C. Bounaix, G. Hanouna, et al., “MAIT Cells Altered Phenotype and Cytotoxicity in lupus Patients Are Linked to Renal Disease Severity and Outcome,” Frontiers in Immunology 14 (2023): 1205405.

[132] N. Hagberg, M. Joelsson, D. Leonard, et al., “The STAT4 SLE Risk Allele rs7574865[T] Is Associated With Increased IL-12-induced IFN-γ Production in T Cells From Patients With SLE,” Annals of the Rheumatic Diseases 77, no. 7 (2018): 1070-1077.

[133] F. Al-Rashed, S. Sindhu, H. Arefanian, et al., “Repetitive Intermittent Hyperglycemia Drives the M1 Polarization and Inflammatory Responses in THP-1 Macrophages Through the Mechanism Involving the TLR4-IRF5 Pathway,” Cells 9, no. 8 (2020): 1892.

[134] K. Soloviova, M. Puliaiev, M. Haas, C. L. Dalgard, B. C. Schaefer, and C. S. Via, “Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-Into-F1 Murine Lupus by Skewing the Immune Response either Toward Help for B Cells and a Sustained Autoantibody Response or Toward Help for CD8 T Cells and a Downregulatory Th1 Response,” Journal of Immunology 195, no. 7 (2015): 2985-3000.

[135] A. Suárez-Fueyo, S. J. Bradley, and G. C. Tsokos, “T Cells in Systemic Lupus erythematosus,” Current Opinion in Immunology 43 (2016): 32-38.

[136] R. Hisada, N. Yoshida, M. Umeda, et al., “The Deacetylase SIRT2 Contributes to Autoimmune Disease Pathogenesis by Modulating IL-17A and IL-2 Transcription,” Cellular & Molecular Immunology 19, no. 6 (2022): 738-750.

[137] Q. Xing, B. Wang, H. Su, J. Cui, and J. Li, “Elevated Th17 Cells Are Accompanied by FoxP3+ Treg Cells Decrease in Patients With Lupus Nephritis,” Rheumatology International 32, no. 4 (2012): 949-958.

[138] M. Scherlinger, W. Pan, R. Hisada, et al., “Phosphofructokinase P Fine-tunes T Regulatory Cell Metabolism, Function, and Stability in Systemic Autoimmunity,” Science Advances 8, no. 48 (2022): eadc9657.

[139] M. Scherlinger, V. Guillotin, I. Douchet, et al., “Selectins Impair Regulatory T Cell Function and Contribute to Systemic Lupus Erythematosus Pathogenesis,” Science Translational Medicine 13, no. 600 (2021): eabi4994.

[140] N. Simpson, P. A. Gatenby, A. Wilson, et al., “Expansion of Circulating T Cells Resembling Follicular Helper T Cells Is a Fixed Phenotype That Identifies a Subset of Severe Systemic Lupus Erythematosus,” Arthritis and Rheumatism 62, no. 1 (2010): 234-244.

[141] X. Huang, S. Hao, J. Liu, et al., “The Ubiquitin Ligase Peli1 Inhibits ICOS and Thereby Tfh-mediated Immunity,” Cellular & Molecular Immunology 18, no. 4 (2021): 969-978.

[142] X. Li, W. Sun, M. Huang, et al., “Deficiency of CBL and CBLB Ubiquitin Ligases Leads to Hyper T Follicular Helper Cell Responses and Lupus by Reducing BCL6 Degradation,” Immunity 57, no. 7 (2024): 1603-1617. e7.

[143] Z. Zhao, B. Xu, S. Wang, et al., “Tfh Cells With NLRP3 Inflammasome Activation Are Essential for High-affinity Antibody Generation, Germinal Centre Formation and Autoimmunity,” Annals of the Rheumatic Diseases 81, no. 7 (2022): 1006-1012.

[144] A. V. Bocharnikov, J. Keegan, V. S. Wacleche, et al., “PD-1hiCXCR5- T Peripheral Helper Cells Promote B Cell Responses in Lupus via MAF and IL-21,” JCI Insight 4, no. 20 (2019): e130062.

[145] S. Tanemura, N. Seki, H. Tsujimoto, et al., “Role of Interferons (IFNs) in the Differentiation of T Peripheral Helper (Tph) Cells,” International Immunology 34, no. 10 (2022): 533-544.

[146] G. S. Dunlap, A. C. Billi, X. Xing, et al., “Single-cell Transcriptomics Reveals Distinct Effector Profiles of Infiltrating T Cells in Lupus Skin and Kidney,” JCI Insight 7, no. 8 (2022): e156341.

[147] E. Pontarini, W. J. Murray-Brown, C. Croia, et al., “Unique Expansion of IL-21+ Tfh and Tph Cells Under Control of ICOS Identifies sjögren's Syndrome With Ectopic Germinal Centres and MALT Lymphoma,” Annals of the Rheumatic Diseases 79, no. 12 (2020): 1588-1599.

[148] C. Law, V. S. Wacleche, Y. Cao, et al., “Interferon Subverts an AHR-JUN Axis to Promote CXCL13+ T Cells in Lupus,” Nature 631, no. 8022 (2024): 857-866.

[149] C. Havenar-Daughton, M. Lindqvist, A. Heit, et al., “CXCL13 is a Plasma Biomarker of Germinal Center Activity,” PNAS 113, no. 10 (2016): 2702-2707.

[150] A. Hoi, T. Igel, C. C. Mok, and L. Arnaud, “Systemic lupus erythematosus,” Lancet 403, no. 10441 (2024): 2326-2338.

[151] P. M. Chen and G. C. Tsokos, “The Role of CD8+ T-cell Systemic Lupus Erythematosus Pathogenesis: An Update,” Current Opinion in Rheumatology 33, no. 6 (2021): 586-591.

[152] E. Katsuyama, A. Suarez-Fueyo, S. J. Bradley, et al., “The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients With SLE Prone to Infections,” Cell Reports 30, no. 1 (2020): 112-123. e4.

[153] P. M. Chen, E. Katsuyama, A. Satyam, et al., “CD38 reduces Mitochondrial Fitness and Cytotoxic T Cell Response Against Viral Infection in lupus Patients by Suppressing Mitophagy,” Science Advances 8, no. 24 (2022): eabo4271.

[154] N. Buang, L. Tapeng, V. Gray, et al., “Type I Interferons Affect the Metabolic Fitness of CD8+ T Cells From Patients With Systemic Lupus Erythematosus,” Nature Communications 12, no. 1 (2021): 1980.

[155] L. Zhang, F. Du, Q. Jin, et al., “Identification and Characterization of CD8+ CD27+ CXCR3− T Cell Dysregulation and Progression-associated Biomarkers in Systemic Lupus Erythematosus,” Advanced Science (Weinh) 10, no. 35 (2023): 2300123.

[156] J. Suurmond, Y. Atisha-Fregoso, E. Marasco, et al., “Loss of an IgG Plasma Cell Checkpoint in Patients With Lupus,” Journal of Allergy and Clinical Immunology 143, no. 4 (2019): 1586-1597.

[157] G. C. Tsokos, “Autoimmunity and Organ Damage in Systemic Lupus erythematosus,” Nature Immunology 21, no. 6 (2020): 605-614.

[158] D. Nikolopoulos, T. Manolakou, A. Polissidis, et al., “Microglia Activation in the Presence of Intact Blood-brain Barrier and Disruption of Hippocampal Neurogenesis via IL-6 and IL-18 Mediate Early Diffuse Neuropsychiatric Lupus,” Annals of the Rheumatic Diseases 82, no. 5 (2023): 646-657.

[159] M. P. Cancro, “Age-associated B Cells,” Annual Review of Immunology 38, no. 1 (2020): 315-340.

[160] M. Manni, S. Gupta, E. Ricker, et al., “Regulation of Age-associated B Cells by IRF5 in Systemic Autoimmunity,” Nature Immunology 19, no. 4 (2018): 407-419.

[161] D. Dai, S. Gu, X. Han, et al., “The Transcription Factor ZEB2 Drives the Formation of Age-associated B Cells,” Science 383, no. 6681 (2024): 413-421.

[162] E. Zumaquero, S. L. Stone, C. D. Scharer, et al., “IFNγ Induces Epigenetic Programming of human T-bethi B Cells and Promotes TLR7/8 and IL-21 Induced Differentiation,” Elife 8 (2019): e41641.

[163] S. A. Jenks, K. S. Cashman, E. Zumaquero, et al., “Distinct Effector B Cells Induced by Unregulated Toll-Like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus,” Immunity 49, no. 4 (2018): 725-739. e6.

[164] G. J. Brown, P. F. Cañete, H. Wang, et al., “TLR7 gain-of-function Genetic Variation Causes human Lupus,” Nature 605, no. 7909 (2022): 349-356.

[165] J. Henault, J. M. Riggs, J. L. Karnell, et al., “Self-reactive IgE Exacerbates Interferon Responses Associated With Autoimmunity,” Nature Immunology 17, no. 2 (2016): 196-203.

[166] K. Ma, W. Du, S. Wang, et al., “B1-cell-produced Anti-phosphatidylserine Antibodies Contribute to Lupus Nephritis Development via TLR-mediated Syk Activation,” Cellular & Molecular Immunology 20, no. 8 (2023): 881-894.

[167] C. E. Faliti, R. Gualtierotti, E. Rottoli, et al., “P2×7 receptor Restrains Pathogenic Tfh Cell Generation in Systemic Lupus Erythematosus,” Journal of Experimental Medicine 216, no. 2 (2019): 317-336.

[168] J. L. Halliley, C. M. Tipton, J. Liesveld, et al., “Long-lived Plasma Cells Are Contained Within the CD19−CD38hiCD138+ Subset in human Bone Marrow,” Immunity 43, no. 1 (2015): 132-145.

[169] R. Vasconcellos, D. Braun, A. Coutinho, and J. Demengeot, “Type I IFN Sets the Stringency of B Cell Repertoire Selection in the Bone Marrow,” International Immunology 11, no. 2 (1999): 279-288.

[170] P. P. Domeier, S. B. Chodisetti, S. L. Schell, et al., “B-cell-intrinsic Type 1 Interferon Signaling Is Crucial for Loss of Tolerance and the Development of Autoreactive B Cells,” Cell Reports 24, no. 2 (2018): 406-418.

[171] J. S. Shim, E. J. Kim, L. E. Lee, et al., “The Oxidative Phosphorylation Inhibitor IM156 Suppresses B-cell Activation by Regulating Mitochondrial Membrane Potential and Contributes to the Mitigation of Systemic Lupus Erythematosus,” Kidney International 103, no. 2 (2023): 343-356.

[172] S. Liu, J. Lagos, N. M. Shumlak, et al., “NADPH Oxidase Exerts a B Cell-intrinsic Contribution to Lupus Risk by Modulating Endosomal TLR Signals,” Journal of Experimental Medicine 221, no. 4 (2024): e20230774.

[173] S. Wang, H. Han, Y. Qian, et al., “Aberrant METTL1-mediated tRNA m7G Modification Alters B-cell Responses in Systemic Autoimmunity in Humans and Mice,” Nature Communications 15, no. 1 (2024): 10599.

[174] H. F. Bradford, T. C. R. McDonnell, A. Stewart, et al., “Thioredoxin Is a Metabolic Rheostat Controlling Regulatory B Cells,” Nature Immunology 25, no. 5 (2024): 873-885.

[175] L. Wang, H. Yin, J. Jiang, et al., “A Rationally Designed CD19 Monoclonal Antibody-triptolide Conjugate for the Treatment of Systemic Lupus Erythematosus,” Acta Pharmaceutica Sinica B 14, no. 10 (2024): 4560-4576.

[176] S. Y. Chu, E. Pong, C. Bonzon, et al., “Inhibition of B Cell Activation Following in Vivo co-engagement of B Cell Antigen Receptor and Fcγ Receptor IIb in Non-autoimmune-prone and SLE-prone Mice,” Journal of Translational Autoimmunity 4 (2021): 100075.

[177] J. T. Merrill, J. Guthridge, M. Smith, et al., “Obexelimab in Systemic Lupus erythematosus With Exploration of Response Based on Gene Pathway co-expression Patterns: A Double-blind, Randomized, Placebo-controlled, Phase 2 Trial,” Arthritis & Rheumatology 75, no. 12 (2023): 2185-2194.

[178] A. D. Marinov, H. Wang, S. I. Bastacky, et al., “The Type II Anti-CD20 Antibody Obinutuzumab (GA101) Is More Effective Than rituximab at Depleting B Cells and Treating Disease in a Murine Lupus Model,” Arthritis & Rheumatology 73, no. 5 (2021): 826-836.

[179] R. A. Furie, G. Aroca, M. D. Cascino, et al., “B-cell Depletion With obinutuzumab for the Treatment of Proliferative Lupus Nephritis: A Randomised, Double-blind, Placebo-controlled Trial,” Annals of the Rheumatic Diseases 81, no. 1 (2022): 100-107.

[180] L. S. Evans, K. E. Lewis, D. DeMonte, et al., “Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-related Autoimmune Diseases,” Arthritis & Rheumatology 75, no. 7 (2023): 1187-1202.

[181] R. Davies, S. L. Peng, J. Lickliter, et al., “A First-in-human, Randomized Study of the Safety, Pharmacokinetics and Pharmacodynamics of Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Healthy Adults,” Clinical and Translational Science 17, no. 11 (2024): e70055.

[182] D. Isenberg, R. Furie, N. S. Jones, et al., “Efficacy, Safety, and Pharmacodynamic Effects of the bruton's Tyrosine Kinase Inhibitor fenebrutinib (GDC-0853) in Systemic lupus erythematosus: Results of a Phase II, Randomized, Double-blind, Placebo-controlled Trial,” Arthritis & Rheumatology 73, no. 10 (2021): 1835-1846.

[183] A. Mackensen, F. Müller, D. Mougiakakos, et al., “Anti-CD19 CAR T Cell Therapy for Refractory Systemic Lupus Erythematosus,” Nature Medicine 28, no. 10 (2022): 2124-2132.

[184] F. Müller, J. Taubmann, L. Bucci, et al., “CD19 CAR T-cell Therapy in Autoimmune Disease—A Case Series With Follow-up,” New England Journal of Medicine 390, no. 8 (2024): 687-700.

[185] X. He, B. Hu, Y. Zhang, et al., “Treatment of Two Pediatric Patients With Refractory Systemic Lupus Erythematosus Using CD19-targeted CAR T-cells,” Autoimmunity Reviews 24, no. 1 (2025): 103692.

[186] M. Hagen, F. Müller, A. Wirsching, et al., “Treatment of CNS Systemic Lupus Erythematosus With CD19 CAR T Cells,” Lancet 404, no. 10468 (2024): 2158-2160.

[187] K. Chen, Y. Deng, S. Shang, et al., “Complement Factor B Inhibitor LNP023 Improves Lupus Nephritis in MRL/Lpr Mice,” Biomedicine & Pharmacotherapy 153 (2022): 113433.

[188] Biogen, “A Study to Learn About the Safety of litifilimab (BIIB059) Injections and Whether They Can Improve Symptoms of Adult Participants Who Have Systemic Lupus Erythematosus (TOPAZ-2),” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT04961567.

[189] Biogen, “A Study to Learn About the Safety of litifilimab (BIIB059) Injections and Whether They Can Improve Symptoms of Adult Participants Who Have Systemic Lupus Erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/ct2/show/NCT04895241.

[190] Biogen, “An Extension Study to Learn More About the Long-term Safety of litifilimab (BIIB059) Injections and Whether They Can Improve Symptoms of Adult Participants Who Have Systemic Lupus Erythematosus (EMERALD)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05352919.

[191] Eisai Co., Ltd., “A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E6742 in Systemic Lupus Erythematosus Participants” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05278663.

[192] Zenas BioPharma (USA), LLC, “A Study of obexelimab in Patients With Systemic Lupus Erythematosus (SunStone)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06559163.

[193] Hoffmann-La Roche, “A Study to Evaluate the Efficacy and Safety of obinutuzumab in Patients With ISN/RPS 2003 Class III or IV Lupus Nephritis (REGENCY)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT04221477.

[194] Peking Union Medical College Hospital, “Efficacy and Safety of Telitacicept in Early SLE” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05899907.

[195] F. Li, “Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05666336.

[196] S. Li, “A Clinical Study on the Effect of Telitacicept on Lymphocyte Subsets in the Treatment of Moderate to Severe Active Systemic Lupus Erythematosus” Chictr.org.cn, accessed May 6, 2025, https://www.chictr.org.cn/showproj.html?proj=207784.

[197] M. Van Schaik, E. J. Arends, D. Soonawala, et al., “Efficacy of belimumab Combined With rituximab in Severe Systemic Lupus Erythematosus: Study Protocol for the Phase 3, Multicenter, Randomized, Open-label synbiose 2 Trial,” Trials 23, no. 1 (2022): 939.

[198] The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, “The Study of Comparing the Efficacy and Safety of human Umbilical Cord MSCs and Low-dose IL-2 in the Treatment of LN” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05631717.

[199] L. Tian, “Efficacy and Immunological Evaluation of Telitacicept and Low Dose IL2 in the Treatment of Systemic Lupus Erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05339217.

[200] Peking University People's Hospital, “Efficacy and Immunological Evaluation of belimumab plus Low Dose IL-2 in the Treatment of Systemic Lupus Erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05262686.

[201] Cugene Inc., “A Phase Ia Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered CUG252 in Normal Healthy Volunteers” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05328557.

[202] UCB Biopharma SRL, “A Study to Evaluate the Safety and Tolerability of Dapirolizumab Pegol in Study Participants With Systemic Lupus Erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT04976322.

[203] Assiut University, “Efficiency of Use of baracetinib in Treatment of Lupus Nephritis” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05432531.

[204] Bristol-Myers Squibb, “A Study to Evaluate Effectiveness and Safety of deucravacitinib (BMS-986165) Compared With Placebo in Participants With Active Systemic Lupus Erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05620407.

[205] AstraZeneca, “An Efficacy and Safety Study of Intravenous Anifrolumab to Treat Systemic Lupus Erythematosus in Pediatric Participants (BLOSSOM)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05835310.

[206] AstraZeneca, “Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis(IRIS)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05138133.

[207] Q. Lu, “Fecal Microbiota Transplantation in the Treatment of Active Systemic Lupus Erythematosus: A Randomized, Double-blind, Placebo-controlled, National Multi-center Clinical Trial,” chictr.org.cn, accessed May 6, 2025, https://www.chictr.org.cn/showproj.html?proj=136062.

[208] Shanghai Ming Ju Biotechnology Co., Ltd., “CD19-CART(relma-cel) for Moderate to Severe Active Systemic Lupus Erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05765006.

[209] Miltenyi Biomedicine GmbH, “MB-CART19.1 in Refractory SLE” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06189157.

[210] Columbia University, “A Study of NKX019, a CD19 CAR NK Cell Therapy, in Subjects With Systemic Lupus Erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06518668.

[211] Second Affiliated Hospital, School of Medicine, Zhejiang University, “Anti-CD19 CAR-NK Cells in Refractory/Relapsed Systemic Lupus Erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06421701.

[212] The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, “IMPT-514 in Systemic Lupus Erythematosus, Anca-associated Vasculitis, and Idiopathic Inflammatory Myopathy” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06462144.

[213] RenJi Hospital, “JWCAR201 for the Treatment of Hematology Malignancy and Autoimmune Diseases,” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06567080.

[214] Essen Biotech, “Sequential CAR-T Cells Targeting BCMA/CD19 in Patients With Relapsed/Refractory Autoimmune Diseases” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06428188.

[215] Essen Biotech, “Fourth-gen CAR T Cells Targeting BCMA/CD19 for Refractory Systemic Lupus Eythematosus (SLE)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06350110.

[216] Guangdong Ruishun Biotech Co., Ltd, “A Study of RJMty19 in Refractory Systemic Lupus Erythematosus (SLE)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06340490.

[217] Novartis Pharmaceuticals, “Study of Efficacy and Safety of LNP023 in Participants With Active Lupus Nephritis Class III-IV, ± V” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05268289.

[218] S. T. Ishizaka, L. Hawkins, Q. Chen, et al., “A Novel Toll-Like Receptor 7/8-specific Antagonist E6742 Ameliorates Clinically Relevant Disease Parameters in Murine Models of Lupus,” European Journal of Pharmacology 957 (2023): 175962.

[219] N. Yamakawa, F. Tago, K. Nakai, et al., “First-in-human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E6742, a Dual Antagonist of Toll-Like Receptors 7 and 8, in Healthy Volunteers,” Clinical Pharmacology in Drug Development 12, no. 4 (2023): 363-375.

[220] D. Szili, M. Cserhalmi, Z. Bankó, G. Nagy, D. E. Szymkowski, and G. Sármay, “Suppression of Innate and Adaptive B Cell Activation Pathways by Antibody Coengagement of FcγRIIb and CD19,” Mabs 6, no. 4 (2014): 991-999.

[221] H. M. Horton, S. Y. Chu, E. C. Ortiz, et al., “Antibody-mediated Coengagement of FcγRIIb and B Cell Receptor Complex Suppresses Humoral Immunity in Systemic Lupus Erythematosus,” Journal of Immunology 186, no. 7 (2011): 4223-4233.

[222] E. Krustev, A. E. Clarke, and M. R. W. Barber, “B Cell Depletion and Inhibition in Systemic Lupus Erythematosus,” Expert Review of Clinical Immunology 19, no. 1 (2023): 55-70.

[223] M. R. Smith, “Rituximab (monoclonal anti-CD20 antibody): Mechanisms of Action and Resistance,” Oncogene 22, no. 47 (2003): 7359-7368.

[224] J. T. Merrill, C. M. Neuwelt, D. J. Wallace, et al., “Efficacy and Safety of rituximab in Moderately-to-severely Active Systemic Lupus Erythematosus: The Randomized, Double-blind, Phase Ii/Iii Systemic Lupus Erythematosus Evaluation of rituximab Trial,” Arthritis and Rheumatism 62, no. 1 (2010): 222-233.

[225] B. H. Rovin, R. Furie, K. Latinis, et al., “Efficacy and Safety of rituximab in Patients With Active Proliferative Lupus Nephritis: The Lupus Nephritis Assessment With rituximab Study,” Arthritis and Rheumatism 64, no. 4 (2012): 1215-1226.

[226] F. Alshaiki, E. Obaid, A. Almuallim, R. Taha, H. El-Haddad, and H. Almoallim, “Department of Medicine, East Jeddah Hospital, Jeddah, Saudi Arabia, Department of Medicine, East Jeddah Hospital, Jeddah, Saudi Arabia, Outcomes of rituximab Therapy in Refractory Lupus: A Meta-analysis,” European Journal of Rheumatology 5, no. 2 (2018): 118-126.

[227] C. Díaz-Lagares, S. Croca, S. Sangle, et al., “Efficacy of rituximab in 164 Patients With Biopsy-proven Lupus Nephritis: Pooled Data From european Cohorts,” Autoimmunity Reviews 11, no. 5 (2012): 357-364.

[228] A. Fanouriakis, M. Kostopoulou, J. Andersen, et al., “EULAR Recommendations for the Management of Systemic Lupus Erythematosus: 2023 Update,” Annals of the Rheumatic Diseases 83, no. 1 (2024): 15-29.

[229] M. Stockfelt, Y. K. O. Teng, and E. M. Vital, “Opportunities and Limitations of B Cell Depletion Approaches in SLE,” Nature Reviews Rheumatology 21, no. 2 (2025): 111-126.

[230] N. Pongtarakulpanit, P. Pisitkun, and P. Ngamjanyaporn, “Efficacy and Safety of rituximab Biosimilar in Refractory Lupus,” Lupus Science & Medicine 7, no. 1 (2020): e000442.

[231] P. Cobb, D. Niederwieser, S. Cohen, et al., “A Review of the Totality of Evidence in the Development of ABP 798, a rituximab Biosimilar,” Immunotherapy 14, no. 9 (2022): 727-740.

[232] J. P. Sharman, A. M. Liberati, K. Ishizawa, et al., “A Randomized, Double-blind, Efficacy and Safety Study of PF-05280586 (a rituximab biosimilar) Compared With rituximab Reference Product (MabThera®) in Subjects With Previously Untreated CD20-positive, Low-tumor-burden Follicular Lymphoma (LTB-FL),” Biodrugs 34, no. 2 (2020): 171-181.

[233] M. G. Tektonidou, A. Dasgupta, and M. M. Ward, “Risk of End-stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and bayesian Meta-analysis,” Arthritis & Rheumatology 68, no. 6 (2016): 1432-1441.

[234] C. L. Freeman and L. H. Sehn, “A Tale of Two Antibodies: Obinutuzumab versus rituximab,” British Journal of Haematology 182, no. 1 (2018): 29-45.

[235] R. Marcus, A. Davies, K. Ando, et al., “Obinutuzumab for the First-line Treatment of Follicular Lymphoma,” New England Journal of Medicine 377, no. 14 (2017): 1331-1344.

[236] W. Townsend, W. Hiddemann, C. Buske, et al., “Obinutuzumab versus rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study,” Hemasphere 7, no. 7 (2023): e919.

[237] J. Arnold, S. Dass, S. Twigg, et al., “Efficacy and Safety of obinutuzumab in Systemic lupus erythematosus Patients With Secondary Non-response to rituximab,” Rheumatology 61, no. 12 (2022): 4905-4909.

[238] L. Bologna, E. Gotti, F. Da Roit, et al., “Ofatumumab Is More Efficient Than rituximab in Lysing B Chronic Lymphocytic Leukemia Cells in Whole Blood and in Combination With Chemotherapy,” Journal of Immunology 190, no. 1 (2013): 231-239.

[239] S. L. Hauser, A. Bar-Or, J. A. Cohen, et al., “Ofatumumab versus Teriflunomide in Multiple Sclerosis,” New England Journal of Medicine 383, no. 6 (2020): 546-557.

[240] J. Gärtner, S. L. Hauser, A. Bar-Or, et al., “Efficacy and Safety of ofatumumab in Recently Diagnosed, Treatment-naive Patients With Multiple Sclerosis: Results From ASCLEPIOS I and II,” Multiple Sclerosis 28, no. 10 (2022): 1562-1575.

[241] J. L. Teeling, W. J. M. Mackus, L. Wiegman, et al., “The Biological Activity of human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20,” Journal of Immunology 177, no. 1 (2006): 362-371.

[242] M. L. Haarhaus, E. Svenungsson, and I. Gunnarsson, “Ofatumumab Treatment in Lupus Nephritis Patients,” Clinical Kidney Journal 9, no. 4 (2016): 552-555.

[243] S. Masoud, S. P. McAdoo, R. Bedi, T. D. Cairns, and L. Lightstone, “Ofatumumab for B Cell Depletion in Patients With Systemic lupus erythematosus Who Are Allergic to rituximab,” Rheumatology 57, no. 7 (2018): 1156-1161.

[244] L. Lei, S. Muhammad, M. Al-Obaidi, et al., “Successful Use of ofatumumab in Two Cases of Early-onset Juvenile SLE With Thrombocytopenia Caused by a Mutation in Protein Kinase C δ,” Pediatric Rheumatology 16, no. 1 (2018): 61.

[245] E. Materne, H. Choi, B. Zhou, K. H. Costenbader, Y. Zhang, and A. Jorge, “Comparative Risks of Infection With belimumab versus Oral Immunosuppressants in Patients With Nonrenal Systemic Lupus Erythematosus,” Arthritis & Rheumatology 75, no. 11 (2023): 1994-2002.

[246] EMD Serono, “Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT00624338.

[247] D. J. Wallace, D. A. Isenberg, E. F. Morand, et al., “Safety and Clinical Activity of atacicept in the Long-term Extension of the Phase 2b ADDRESS II Study in Systemic Lupus Erythematosus,” Rheumatology 60, no. 11 (2021): 5379-5389.

[248] D. Wu, J. Li, D. Xu, et al., “Telitacicept in Patients With Active Systemic Lupus Erythematosus: Results of a Phase 2b, Randomised, Double-blind, Placebo-controlled Trial,” Annals of the Rheumatic Diseases 83, no. 4 (2024): 475-487.

[249] Alpine Immune Sciences, Inc., “A Study of ALPN-303 in Adult Healthy Volunteers (RUBY-1)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05034484.

[250] M. R. Ehrenstein and C. Wing, “The BAFFling Effects of rituximab in lupus: Danger Ahead?,” Nature Reviews Rheumatology 12, no. 6 (2016): 367-372.

[251] T. Kraaij, S. W. A. Kamerling, E. N. M. De Rooij, et al., “The NET-effect of Combining rituximab With belimumab in Severe Systemic Lupus Erythematosus,” Journal of Autoimmunity 91 (2018): 45-54.

[252] M. Shipa, A. Embleton-Thirsk, M. Parvaz, et al., “Effectiveness of belimumab After rituximab in Systemic lupus erythematosus: A Randomized Controlled Trial,” Annals of Internal Medicine 174, no. 12 (2021): 1647-1657.

[253] Bristol-Myers Squibb, “Efficacy and Safety Study of abatacept to Treat Lupus Nephritis” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT00430677.

[254] J. Y. Humrich, C. Von Spee-Mayer, E. Siegert, et al., “Low-dose Interleukin-2 Therapy in Refractory Systemic Lupus Erythematosus: An Investigator-initiated, Single-centre Phase 1 and 2a Clinical Trial,” The Lancet Rheumatology 1, no. 1 (2019): e44-e54.

[255] J. He, R. Zhang, M. Shao, et al., “Efficacy and Safety of Low-dose IL-2 in the Treatment of Systemic Lupus Erythematosus: A Randomised, Double-blind, Placebo-controlled Trial,” Annals of the Rheumatic Diseases 79, no. 1 (2020): 141-149.

[256] J. He, X. Zhang, Y. Wei, et al., “Low-dose Interleukin-2 Treatment Selectively Modulates CD4+ T Cell Subsets in Patients With Systemic Lupus Erythematosus,” Nature Medicine 22, no. 9 (2016): 991-993.

[257] K. Liang, J. He, Y. Wei, et al., “Sustained Low-dose Interleukin-2 Therapy Alleviates Pathogenic Humoral Immunity via Elevating the Tfr/Tfh Ratio in Lupus,” Clinical & Translational Immunology 10, no. 6 (2021): e1293.

[258] M. Rosenzwajg, R. Lorenzon, P. Cacoub, et al., “Immunological and Clinical Effects of Low-dose Interleukin-2 Across 11 Autoimmune Diseases in a Single, Open Clinical Trial,” Annals of the Rheumatic Diseases 78, no. 2 (2019): 209-217.

[259] Peking University People's Hospital, “Low-dose IL-2 (interleukin-2) Treatment in SLE” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT02084238.

[260] J. Y. Humrich, P. Cacoub, M. Rosenzwajg, et al., “Low-dose Interleukin-2 Therapy in Active Systemic Lupus erythematosus (LUPIL-2): A Multicentre, Double-blind, Randomised and Placebo-controlled Phase II Trial,” Annals of the Rheumatic Diseases 81, no. 12 (2022): 1685-1694.

[261] H. Zhou, X. Zhao, R. Zhang, et al., “Low-dose IL-2 Mitigates Glucocorticoid-induced Treg Impairment and Promotes Improvement of SLE,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 141.

[262] Amgen, “Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Efavaleukin alfa in Participants With Systemic lupus erythematosus” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT03451422.

[263] Nektar Therapeutics, “A Study of LY3471851 in Adults With Systemic Lupus Erythematosus (SLE)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT04433585.

[264] Novartis Pharmaceuticals, “Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT03656562.

[265] Boehringer Ingelheim, “An Exploratory Maintenance Trial of BI 655064 in Patients With Lupus Nephritis” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT03385564.

[266] D. R. Jayne, J. Steffgen, J. Romero-Diaz, et al., “Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-blind, Placebo-controlled, Phase II Trial,” Arthritis & Rheumatology 75, no. 11 (2023): 1983-1993.

[267] L. E. Cheng, Z. Amoura, B. Cheah, et al., “Brief Report: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multiple-dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis,” Arthritis & Rheumatology 70, no. 7 (2018): 1071-1076.

[268] D. J. Wallace, R. A. Furie, Y. Tanaka, et al., “Baricitinib for Systemic Lupus Erythematosus: A Double-blind, Randomised, Placebo-controlled, Phase 2 Trial,” Lancet 392, no. 10143 (2018): 222-231.

[269] E. F. Morand, E. M. Vital, M. Petri, et al., “Baricitinib for Systemic Lupus Erythematosus: A Double-blind, Randomised, Placebo-controlled, Phase 3 Trial (SLE-BRAVE-I),” Lancet 401, no. 10381 (2023): 1001-1010.

[270] M. Petri, I. N. Bruce, T. Dörner, et al., “Baricitinib for Systemic Lupus Erythematosus: A Double-blind, Randomised, Placebo-controlled, Phase 3 Trial (SLE-BRAVE-II),” Lancet 401, no. 10381 (2023): 1011-1019.

[271] E. Morand, M. Pike, J. T. Merrill, et al., “Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-blind, Placebo-controlled Trial,” Arthritis & Rheumatology 75, no. 2 (2023): 242-252.

[272] D. Jayne, B. Rovin, E. F. Mysler, et al., “Phase II Randomised Trial of Type I Interferon Inhibitor anifrolumab in Patients With Active Lupus Nephritis,” Annals of the Rheumatic Diseases 81, no. 4 (2022): 496-506.

[273] K. Ghoreschi, A. Balato, C. Enerbäck, and R. Sabat, “Therapeutics Targeting the IL-23 and IL-17 Pathway in Psoriasis,” Lancet 397, no. 10275 (2021): 754-766.

[274] A. Danve and A. Deodhar, “Treatment of Axial Spondyloarthritis: An Update,” Nature Reviews Rheumatology 18, no. 4 (2022): 205-216.

[275] T. Koga, K. Ichinose, A. Kawakami, and G. C. Tsokos, “The Role of IL-17 in Systemic Lupus Erythematosus and Its Potential as a Therapeutic Target,” Expert Review of Clinical Immunology 15, no. 6 (2019): 629-637.

[276] P. Ávila-Ribeiro, A. R. Lopes, J. Martins-Martinho, et al., “Secukinumab-induced Systemic Lupus Erythematosus in Psoriatic Arthritis,” ARP Rheumatology 2, no. 3 (2023): 265-268.

[277] J. Kaler and G. S. Kaeley, “Secukinumab-induced Lupus erythematosus: A Case Report and Literature Review,” Journal of Clinical Rheumatology 27, no. 8S (2021): S753-S754.

[278] Novartis Pharmaceuticals, “Open-label Extension Study of Efficacy, Safety and Tolerability of secukinumab in Patients With Active Lupus Nephritis” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT05232864.

[279] Suzhou Suncadia Biopharmaceuticals Co., Ltd., “A Phase II Study to Evaluate the Efficacy and Safety of SHR-1314 in Lupus Nephritis” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT04924296.

[280] A. Katewa, Y. Wang, J. A. Hackney, et al., “Btk-specific Inhibition Blocks Pathogenic Plasma Cell Signatures and Myeloid Cell-associated Damage in IFNα-driven Lupus Nephritis,” JCI Insight 2, no. 7 (2017): e90111.

[281] F. N. C. Kalayci and S. Ozen, “Possible Role of Dysbiosis of the Gut Microbiome in SLE,” Current Rheumatology Reports 25, no. 12 (2023): 247-258.

[282] D. Azzouz, A. Omarbekova, A. Heguy, et al., “Lupus Nephritis Is Linked to Disease-activity Associated Expansions and Immunity to a Gut Commensal,” Annals of the Rheumatic Diseases 78, no. 7 (2019): 947-956.

[283] Y. Chen, J. Lin, L. Xiao, et al., “Gut Microbiota in Systemic Lupus Erythematosus: A Fuse and a Solution,” Journal of Autoimmunity 132 (2022): 102867.

[284] C. Huang, P. Yi, M. Zhu, et al., “Safety and Efficacy of Fecal Microbiota Transplantation for Treatment of Systemic Lupus Erythematosus: An EXPLORER Trial,” Journal of Autoimmunity 130 (2022): 102844.

[285] Y. Ma, X. Xu, M. Li, J. Cai, Q. Wei, and H. Niu, “Gut Microbiota Promote the Inflammatory Response in the Pathogenesis of Systemic Lupus Erythematosus,” Molecular Medicine 25, no. 1 (2019): 35.

[286] F. Guo, Q. Pan, T. Chen, et al., “hUC-MSC Transplantation Therapy Effects on Lupus-prone MRL/Lpr Mice at Early Disease Stages,” Stem Cell Research & Therapy 14, no. 1 (2023): 211.

[287] L. Sun, D. Wang, J. Liang, et al., “Umbilical Cord Mesenchymal Stem Cell Transplantation in Severe and Refractory Systemic Lupus Erythematosus,” Arthritis and Rheumatism 62, no. 8 (2010): 2467-2475.

[288] D. Deng, P. Zhang, Y. Guo, and T. O. Lim, “A Randomised Double-blind, Placebo-controlled Trial of Allogeneic Umbilical Cord-derived Mesenchymal Stem Cell for Lupus Nephritis,” Annals of the Rheumatic Diseases 76, no. 8 (2017): 1436-1439.

[289] Chinese PLA General Hospital, “Mesenchymal Stem Cell Transfusion for the Treatment of Refractory Lupus Nephritis” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06485648.

[290] A. Alunno, O. Bistoni, P. Montanucci, G. Basta, R. Calafiore, and R. Gerli, “Umbilical Cord Mesenchymal Stem Cells for the Treatment of Autoimmune Diseases: Beware of Cell-to-cell Contact,” Annals of the Rheumatic Diseases 77, no. 3 (2018): e14.

[291] A. Ning, N. Xiao, X. Yu, et al., “Dimethyloxallyl Glycine Preconditioning Promotes the Anti-inflammatory and Anti-fibrotic Effects of human Umbilical Cord Mesenchymal Stem Cells on Kidney Damage in Systemic Lupus Erythematosus Related to TGF-β/Smad Signaling Pathway,” Inflammation 48, no. 2 (2025): 839-854. Published online July 24, 2024.

[292] X. Jin, Q. Xu, C. Pu, et al., “Therapeutic Efficacy of Anti-CD19 CAR-T Cells in a Mouse Model of Systemic Lupus Erythematosus,” Cellular & Molecular Immunology 18, no. 8 (2021): 1896-1903.

[293] R. Kansal, N. Richardson, I. Neeli, et al., “Sustained B Cell Depletion by CD19-targeted CAR T Cells Is a Highly Effective Treatment for Murine Lupus,” Science Translational Medicine 11, no. 482 (2019): eaav1648.

[294] Shanghai Changzheng Hospital, “Anti-CD19-CD3E-CAR-T Cells in Relapsed/​Refractory Autoimmune Disease” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT06373081.

[295] H. Zhang, D. V. Rizk, V. Perkovic, et al., “Results of a Randomized Double-blind Placebo-controlled Phase 2 Study Propose iptacopan as an Alternative Complement Pathway Inhibitor for IgA Nephropathy,” Kidney International 105, no. 1 (2024): 189-199.

[296] Novartis Pharmaceuticals, “Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients (APPLAUSE-IgAN)” ClinicalTrials.gov, accessed May 6, 2025, https://clinicaltrials.gov/study/NCT04578834.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.