Lupus Nephritis: Current Perspectives and Moving Forward

References

• Anders H-J, Saxena R, Zhao M-H, et al. Lupus nephritis. Nat Rev Dis Primers. 2020;6:7. doi:10.1038/s41572-019-0141-9
   PubMed Web of Science ®Google Scholar
• Anders H-J, Fogo AB. Immunopathology of lupus nephritis. Semin Immunopathol. 2014;36:443–459. doi:10.1007/s00281-013-0413-5
   PubMed Web of Science ®Google Scholar
• Lorenz G, Lech M, Anders H-J. Toll-like receptor activation in the pathogenesis of lupus nephritis. Clin Immunol. 2017;185:86–94. doi:10.1016/j.clim.2016.07.015
   PubMed Web of Science ®Google Scholar
• Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol. 2019;71(9):1400–1412. doi:10.1002/art.40930
   PubMed Web of Science ®Google Scholar
• Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT. Update on the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis. 2021;80(1):14–25. doi:10.1136/annrheumdis-2020-218272
   PubMed Web of Science ®Google Scholar
• Steiger S, Rossaint J, Zarbock A, Anders H-J. Secondary Immunodeficiency Related to Kidney Disease (SIDKD)-definition, unmet need, and mechanisms. J Am Soc Nephrol. 2022;33:259–278.
   PubMed Web of Science ®Google Scholar
• Demirkaya E, Sahin S, Romano M, Zhou Q, Aksentijevich I. New horizons in the genetic etiology of systemic lupus erythematosus and lupus-like disease: monogenic lupus and beyond. J Clin Med. 2020;9:E712.
   PubMed Web of Science ®Google Scholar
• Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. Arthritis Res Ther. 2012;14:211. doi:10.1186/ar3844
   PubMed Web of Science ®Google Scholar
• Tiffin N, Adeyemo A, Okpechi I. A diverse array of genetic factors contribute to the pathogenesis of systemic lupus erythematosus. Orphanet J Rare Dis. 2013;8:2. doi:10.1186/1750-1172-8-2
   PubMed Web of Science ®Google Scholar
• Deng Y, Tsao BP. Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat Rev Rheumatol. 2010;6:683–692. doi:10.1038/nrrheum.2010.176
   PubMed Web of Science ®Google Scholar
• Kelley JM, Edberg JC, Kimberly RP. Pathways: strategies for susceptibility genes in SLE. Autoimmun Rev. 2010;9:473–476. doi:10.1016/j.autrev.2010.02.003
   PubMed Web of Science ®Google Scholar
• Rullo OJ, Tsao BP. Recent insights into the genetic basis of systemic lupus erythematosus. Ann Rheum Dis. 2013;72(Suppl 2):ii56–61. doi:10.1136/annrheumdis-2012-202351
   PubMed Web of Science ®Google Scholar
• Costa-Reis P, Sullivan KE. Genetics and epigenetics of systemic lupus erythematosus. Curr Rheumatol Rep. 2013;15:369. doi:10.1007/s11926-013-0369-4
   PubMed Web of Science ®Google Scholar
• Yang F, He Y, Zhai Z, Sun E. Programmed cell death pathways in the pathogenesis of systemic lupus erythematosus. J Immunol Res. 2019;3638562:2019.
   Google Scholar
• Mistry P, Kaplan MJ. Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis. Clin Immunol. 2017;185:59–73. doi:10.1016/j.clim.2016.08.010
   PubMed Web of Science ®Google Scholar
• Hepburn AL, Mason JC, Wang S, et al. Both Fcγ and complement receptors mediate transfer of immune complexes from erythrocytes to human macrophages under physiological flow conditions in vitro. Clin Exp Immunol. 2006;146(1):133–145. doi:10.1111/j.1365-2249.2006.03174.x
   PubMed Web of Science ®Google Scholar
• MacPherson M, Lek HS, Prescott A, Fagerholm SC. A systemic lupus erythematosus-associated R77H substitution in the CD11b chain of the Mac-1 integrin compromises leukocyte adhesion and phagocytosis. J Biol Chem. 2011;286:17303–17310. doi:10.1074/jbc.M110.182998
   PubMed Web of Science ®Google Scholar
• Nath SK, Han S, Kim-Howard X, et al. A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet. 2008;40:152–154. doi:10.1038/ng.71
   PubMed Web of Science ®Google Scholar
• Yang W, Tang H, Zhang Y, et al. Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians. Am J Hum Genet. 2013;92:41–51. doi:10.1016/j.ajhg.2012.11.018
   PubMed Web of Science ®Google Scholar
• Harley JB, Alarcón-Riquelme ME, Criswell LA; 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. Nat Genet. 2008;40:204–210. doi:10.1038/ng.81
   PubMed Web of Science ®Google Scholar
• Freedman BI, Langefeld CD, Andringa KK, et al. End-stage renal disease in African Americans With Lupus Nephritis Is Associated With APOL1. Arthritis Rheumatol. 2014;66:390–396. doi:10.1002/art.38220
   PubMed Web of Science ®Google Scholar
• Zhou X, Lu X-L, Lv J-C, et al. Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis. 2011;70:1330–1337. doi:10.1136/ard.2010.140111
   PubMed Web of Science ®Google Scholar
• Kuma A, Hatano M, Matsui M, et al. The role of autophagy during the early neonatal starvation period. Nature. 2004;432(7020):1032–1036. doi:10.1038/nature03029
   PubMed Web of Science ®Google Scholar
• Gateva V, Sandling JK, Hom G, et al. A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet. 2009;41(11):1228–1233. doi:10.1038/ng.468
   PubMed Web of Science ®Google Scholar
• Allam R, Anders H-J. The role of innate immunity in autoimmune tissue injury. Curr Opin Rheumatol. 2008;20:538–544. doi:10.1097/BOR.0b013e3283025ed4
   PubMed Web of Science ®Google Scholar
• Lech M, Anders H-J. The pathogenesis of lupus nephritis. J Am Soc Nephrol. 2013;24:1357–1366. doi:10.1681/ASN.2013010026
   PubMed Web of Science ®Google Scholar
• Rodero MP, Decalf J, Bondet V, et al. Detection of interferon alpha protein reveals differential levels and cellular sources in disease. J Exp Med. 2017;214(5):1547–1555. doi:10.1084/jem.20161451
   PubMed Web of Science ®Google Scholar
• Nehar-Belaid D, Hong S, Marches R, et al. Mapping systemic lupus erythematosus heterogeneity at the single-cell level. Nat Immunol. 2020;21(9):1094–1106. doi:10.1038/s41590-020-0743-0
   PubMed Web of Science ®Google Scholar
• Banchereau R, Hong S, Cantarel B, et al. Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. Cell. 2016;165(3):551–565. doi:10.1016/j.cell.2016.03.008
   PubMed Web of Science ®Google Scholar
• Gao D, Li T, Li X-D, et al. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. Proc Natl Acad Sci U S A. 2015;112(42):E5699–E5705. doi:10.1073/pnas.1516465112
   PubMed Web of Science ®Google Scholar
• Yoneyama M, Kikuchi M, Matsumoto K, et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol. 2005;175(5):2851–2858. doi:10.4049/jimmunol.175.5.2851
   PubMed Web of Science ®Google Scholar
• Loo Y-M, Gale M. Immune signaling by RIG-I-like receptors. Immunity. 2011;34:680–692. doi:10.1016/j.immuni.2011.05.003
   PubMed Web of Science ®Google Scholar
• Keating SE, Baran M, Bowie AG. Cytosolic DNA sensors regulating type I interferon induction. Trends Immunol. 2011;32:574–581. doi:10.1016/j.it.2011.08.004
   PubMed Web of Science ®Google Scholar
• Radetskyy R, Daher A, Gatignol A. ADAR1 and PKR, interferon stimulated genes with clashing effects on HIV-1 replication. Cytokine Growth Factor Rev. 2018;40:48–58. doi:10.1016/j.cytogfr.2018.03.007
   PubMed Web of Science ®Google Scholar
• Wang TT, Li ZG, Wang Q. The RNA-specific adenosine deaminase ADAR1 Inhibits Human Protein Kinase R Activation. Viral Immunol. 2018;31:537–538. doi:10.1089/vim.2018.0056
   PubMed Web of Science ®Google Scholar
• Patole PS, Zecher D, Pawar RD, et al. G-rich DNA suppresses systemic lupus. J Am Soc Nephrol. 2005;16(11):3273–3280. doi:10.1681/ASN.2005060658
   PubMed Web of Science ®Google Scholar
• Anders HJ. A Toll for lupus. Lupus. 2005;14:417–422. doi:10.1191/0961203305lu2102rr
   PubMed Web of Science ®Google Scholar
• Vance RE. Cytosolic DNA sensing: the field narrows. Immunity. 2016;45:227–228. doi:10.1016/j.immuni.2016.08.006
   PubMed Web of Science ®Google Scholar
• Bolin K, Imgenberg-Kreuz J, Leonard D, et al. Variants in BANK1 are associated with lupus nephritis of European ancestry. Genes Immun. 2021;22(3):194–202. doi:10.1038/s41435-021-00142-8
   PubMed Web of Science ®Google Scholar
• Pisitkun P, Deane JA, Difilippantonio MJ, et al. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science. 2006;312:1669–1672. doi:10.1126/science.1124978
   PubMed Web of Science ®Google Scholar
• Christensen SR, Shupe J, Nickerson K, et al. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity. 2006;25(3):417–428. doi:10.1016/j.immuni.2006.07.013
   PubMed Web of Science ®Google Scholar
• Deane JA, Pisitkun P, Barrett RS, et al. Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity. 2007;27(5):801–810. doi:10.1016/j.immuni.2007.09.009
   PubMed Web of Science ®Google Scholar
• Rönnblom L. The type I interferon system in the etiopathogenesis of autoimmune diseases. Ups J Med Sci. 2011;116:227–237. doi:10.3109/03009734.2011.624649
   PubMed Web of Science ®Google Scholar
• Brown GJ, Cañete PF, Wang H, et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022;605(7909):349–356. doi:10.1038/s41586-022-04642-z
   PubMed Web of Science ®Google Scholar
• Chen M, Daha MR, Kallenberg CGM. The complement system in systemic autoimmune disease. J Autoimmun. 2010;34:J276–J286. doi:10.1016/j.jaut.2009.11.014
   PubMed Web of Science ®Google Scholar
• Stegert M, Bock M, Trendelenburg M. Clinical presentation of human C1q deficiency: how much of a lupus? Mol Immunol. 2015;67:3–11. doi:10.1016/j.molimm.2015.03.007
   PubMed Web of Science ®Google Scholar
• Musone SL, Taylor KE, Lu TT, et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet. 2008;40:1062–1064. doi:10.1038/ng.202
   PubMed Web of Science ®Google Scholar
• Kawasaki A, Ito S, Furukawa H, et al. Association of TNFAIP3 interacting protein 1, TNIP1 with systemic lupus erythematosus in a Japanese population: a case-control association study. Arthritis Res Ther. 2010;12(5):R174. doi:10.1186/ar3134
   PubMed Web of Science ®Google Scholar
• Zhou J, Wu R, High AA, et al. A20-binding inhibitor of NF-κB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein β activation and protects from inflammatory disease. Proc Natl Acad Sci U S A. 2011;108(44):E998–E1006. doi:10.1073/pnas.1106232108
   PubMed Web of Science ®Google Scholar
• Moynihan TP, Cole CG, Dunham I, et al. Fine-mapping, genomic organization, and transcript analysis of the human ubiquitin-conjugating enzyme gene UBE2L3. Genomics. 1998;51(1):124–127. doi:10.1006/geno.1998.5257
   PubMed Web of Science ®Google Scholar
• Kim T, Bae S-C, Kang C. Synergistic activation of NF-κB by TNFAIP3 (A20) reduction and UBE2L3 (UBCH7) augment that synergistically elevate lupus risk. Arthritis Res Ther. 2020;22:93. doi:10.1186/s13075-020-02181-4
   PubMed Web of Science ®Google Scholar
• Liang J, Saad Y, Lei T, et al. MCP-induced protein 1 deubiquitinates TRAF proteins and negatively regulates JNK and NF-kappaB signaling. J Exp Med. 2010;207:2959–2973. doi:10.1084/jem.20092641
   PubMed Web of Science ®Google Scholar
• Dobosz E, Lorenz G, Ribeiro A, et al. Murine myeloid cell MCPIP1 suppresses autoimmunity by regulating B-cell expansion and differentiation. Dis Model Mech. 2021;14(3):dmm047589. doi:10.1242/dmm.047589
   PubMed Web of Science ®Google Scholar
• Caster DJ, Korte EA, Nanda SK, et al. ABIN1 dysfunction as a genetic basis for lupus nephritis. J Am Soc Nephrol. 2013;24(11):1743–1754. doi:10.1681/ASN.2013020148
   PubMed Web of Science ®Google Scholar
• Lech M, Kantner C, Kulkarni OP, et al. Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus. Ann Rheum Dis. 2011;70(12):2207–2217. doi:10.1136/ard.2011.155515
   PubMed Web of Science ®Google Scholar
• Szelinski F, Lino AC, Dörner T. B cells in systemic lupus erythematosus. Curr Opin Rheumatol. 2022;34:125–132. doi:10.1097/BOR.0000000000000865
   PubMed Web of Science ®Google Scholar
• Harley ITW, Allison K, Scofield RH. Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans. Front Immunol. 2022;13:953439.
   PubMed Web of Science ®Google Scholar
• Suárez-Fueyo A, Bradley SJ, Tsokos GC. T cells in Systemic Lupus Erythematosus. Curr Opin Immunol. 2016;43:32–38. doi:10.1016/j.coi.2016.09.001
   PubMed Web of Science ®Google Scholar
• Karimifar M, Akbari K, ArefNezhad R, et al. Impacts of FcγRIIB and FcγRIIIA gene polymorphisms on systemic lupus erythematosus disease activity index. BMC Res Notes. 2021;14(1):455. doi:10.1186/s13104-021-05868-2
   PubMed Web of Science ®Google Scholar
• Rzeszotarska E, Sowinska A, Stypinska B, et al. IL-1β, IL-10 and TNF-α polymorphisms may affect systemic lupus erythematosus risk and phenotype. Clin Exp Rheumatol. 2022;40:1708–1717.
   PubMed Web of Science ®Google Scholar
• Chrabot BS, Kariuki SN, Zervou MI, et al. Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis. Genes Immun. 2013;14(8):471–478. doi:10.1038/gene.2013.42
   PubMed Web of Science ®Google Scholar
• Kim K, Brown EE, Choi CB, et al. Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries. Ann Rheum Dis. 2012;71:1809–1814.
   PubMed Web of Science ®Google Scholar
• Roberts AL, Thomas ER, Bhosle S, et al. Resequencing the susceptibility gene, ITGAM, identifies two functionally deleterious rare variants in systemic lupus erythematosus cases. Arthritis Res Ther. 2014;16(3):R114. doi:10.1186/ar4566
   PubMed Web of Science ®Google Scholar
• Moreno-Angarita A, Aragón CC, Tobón GJ. Cathelicidin LL-37: a new important molecule in the pathophysiology of systemic lupus erythematosus. J Transl Autoimmun. 2020;3:100029.
   PubMedGoogle Scholar
• Borchers AT, Leibushor N, Naguwa SM, et al. Lupus nephritis: a critical review. Autoimmun Rev. 2012;12:174–194.
   PubMed Web of Science ®Google Scholar
• Schwartzman-Morris J, Putterman C. Gender differences in the pathogenesis and outcome of lupus and of lupus nephritis. Clin Dev Immunol. 2012;604892:2012.
   Google Scholar
• Maroz N, Segal MS. Lupus nephritis and end-stage kidney disease. Am J Med Sci. 2013;346:319–323.
   PubMed Web of Science ®Google Scholar
• Chung SA, Taylor KE., Graham RR, et al. Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production. PLoS Genet. 2011;7:e1001323.
   PubMed Web of Science ®Google Scholar
• Freedman BI, Kopp JB, Langefeld CD, et al. The Apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African Americans. J Am Soc Nephrol. 2010;21:1422–1426. doi:10.1681/ASN.2010070730
   PubMed Web of Science ®Google Scholar
• Lin CP, Adrianto I, Lessard CJ, et al. Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis. Genes Immun. 2012;13(3):232–238. doi:10.1038/gene.2011.82
   PubMed Web of Science ®Google Scholar
• Alonso-Perez E, Suarez-Gestal M, Calaza M, et al. Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study. PLoS One. 2012;7(9):e45356. doi:10.1371/journal.pone.0045356
   PubMed Web of Science ®Google Scholar
• Taylor KE, Remmers EF, Lee AT, et al. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus. PLoS Genet. 2008;4:e1000084.
   PubMed Web of Science ®Google Scholar
• Bolin K, Sandling JK, Zickert A, et al. Association of STAT4 polymorphism with severe renal insufficiency in lupus nephritis. PLoS One. 2013;8(12):e84450. doi:10.1371/journal.pone.0084450
   PubMed Web of Science ®Google Scholar
• Zhou X, Cheng F, Qi Y, Zhao M, Zhang H. A replication study from Chinese supports association between lupus-risk allele in TNFSF4 and renal disorder. Biomed Res Int. 2013;597921:2013.
   Google Scholar
• Lanata CM, Nititham J, Taylor KE, et al. Genetic contributions to lupus nephritis in a multi-ethnic cohort of systemic lupus erythematosus patients. PLoS One. 2018;13(6):e0199003. doi:10.1371/journal.pone.0199003
   PubMed Web of Science ®Google Scholar
• Zhang F, Wang Y-F, Zhang Y, et al. Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus. Front Genet. 2020;11:600. doi:10.3389/fgene.2020.00600
   PubMed Web of Science ®Google Scholar
• Dooley MA, Houssiau F, Aranow C, et al. Effect of belimumab treatment on renal outcomes: results from the phase 3 belimumab clinical trials in patients with SLE. Lupus. 2013;22(1):63–72. doi:10.1177/0961203312465781
   PubMed Web of Science ®Google Scholar
• Merrill JT, Neuwelt CM, Wallace DJ, 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 Rheum. 2010;62:222–233.
   PubMed Web of Science ®Google Scholar
• Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012;64(4):1215–1226. doi:10.1002/art.34359
   PubMed Web of Science ®Google Scholar
• Kamburova EG, Koenen HJPM, Borgman KJE, et al. A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function. Am J Transplant. 2013;13:1503–1511. doi:10.1111/ajt.12220
   PubMed Web of Science ®Google Scholar
• Furie RA, Aroca G, Cascino MD, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022;81(1):100–107. doi:10.1136/annrheumdis-2021-220920
   PubMed Web of Science ®Google Scholar
• Mössner E, Brünker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010;115:4393–4402. doi:10.1182/blood-2009-06-225979
   PubMed Web of Science ®Google Scholar
• Haarhaus ML, Svenungsson E, Gunnarsson I. Ofatumumab treatment in lupus nephritis patients. Clin Kidney J. 2016;9:552–555. doi:10.1093/ckj/sfw022
   PubMed Web of Science ®Google Scholar
• Mackensen A, Müller F, Mougiakakos D, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022. doi:10.1038/s41591-022-02017-5
   Web of Science ®Google Scholar
• Mougiakakos D, Krönke G, Völkl S, et al. CD19-targeted CAR T cells in refractory systemic lupus erythematosus. N Engl J Med. 2021;385(6):567–569. doi:10.1056/NEJMc2107725
   PubMed Web of Science ®Google Scholar
• Merrill JT, Wallace DJ, Wax S, et al. Efficacy and safety of atacicept in patients with systemic lupus erythematosus: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm, Phase IIb study. Arthritis Rheumatol. 2018;70(2):266–276. doi:10.1002/art.40360
   PubMed Web of Science ®Google Scholar
• Wu D, Li J, Xu D, et al. A human recombinant fusion protein targeting B lymphocyte stimulator (BlyS) and a proliferation-inducing ligand (April), telitacicept (RC18), in systemic lupus erythematosus (SLE): results of a phase 2b study [abstract no. L18]. Arthritis Rheumatol. 2019;71(Suppl10):5262–5264.
   Google Scholar
• Merrill JT, Van Vollenhoven RF, Buyon JP, et al. Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, Phase III, multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016;75:332–340.
   PubMed Web of Science ®Google Scholar
• Isenberg DA, Petri M, Kalunian K, et al. Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016;75(2):323–331. doi:10.1136/annrheumdis-2015-207653
   PubMed Web of Science ®Google Scholar
• Merrill JT, Shanahan WR, Scheinberg M, et al. Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2018;77(6):883–889. doi:10.1136/annrheumdis-2018-213032
   PubMed Web of Science ®Google Scholar
• Cheng LE, Amoura Z, Cheah B, 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 Rheumatol. 2018;70:1071–1076.
   PubMed Web of Science ®Google Scholar
• Lipsky PE, Vollenhoven RV, Dörner T, et al. Biological impact of iberdomide in patients with active systemic lupus erythematosus. Ann Rheum Dis Annrheumdis. 2022;81(8):1136–1142. doi:10.1136/annrheumdis-2022-222212
   PubMed Web of Science ®Google Scholar
• Merrill JT, Werth VP, Furie R, et al. Phase 2 trial of iberdomide in systemic lupus erythematosus. N Engl J Med. 2022;386:1034–1045.
   PubMed Web of Science ®Google Scholar
• Klimatcheva E, Pandina T, Reilly C, et al. CXCL13 antibody for the treatment of autoimmune disorders. BMC Immunol. 2015;16:6.
   PubMed Web of Science ®Google Scholar
• Hiepe F, Alexander T, Voll RE. Plasmazellen [Plasma cells]. Z Rheumatol. 2015;74:20–25. German. doi:10.1007/s00393-014-1438-4
   PubMed Web of Science ®Google Scholar
• Odendahl M, Mei H, Hoyer BF, et al. Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. Blood. 2005;105(4):1614–1621. doi:10.1182/blood-2004-07-2507
   PubMed Web of Science ®Google Scholar
• Muehlinghaus G, Cigliano L, Huehn S, et al. Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells. Blood. 2005;105(10):3965–3971. doi:10.1182/blood-2004-08-2992
   PubMed Web of Science ®Google Scholar
• Arce S, Luger E, Muehlinghaus G, et al. CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations. J Leukoc Biol. 2004;75(6):1022–1028. doi:10.1189/jlb.0603279
   PubMed Web of Science ®Google Scholar
• Rodríguez-Bayona B, Ramos-Amaya A, Bernal J, Campos-Caro A, Brieva JA. Cutting edge: IL-21 derived from human follicular helper T cells acts as a survival factor for secondary lymphoid organ, but not for bone marrow, plasma cells. J Immunol. 2012;188:1578–1581. doi:10.4049/jimmunol.1102786
   PubMed Web of Science ®Google Scholar
• Kehrl JH, Riva A, Wilson GL, Thévenin C. Molecular mechanisms regulating CD19, CD20 and CD22 gene expression. Immunol Today. 1994;15:432–436. doi:10.1016/0167-5699(94)90273-9
   PubMedGoogle Scholar
• Leandro MJ. B-cell subpopulations in humans and their differential susceptibility to depletion with anti-CD20 monoclonal antibodies. Arthritis Res Ther. 2013;15(Suppl 1):S3. doi:10.1186/ar3908
   PubMed Web of Science ®Google Scholar
• Hoyer BF, Moser K, Hauser AE, et al. Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. J Exp Med. 2004;199(11):1577–1584. doi:10.1084/jem.20040168
   PubMed Web of Science ®Google Scholar
• Neubert K, Meister S, Moser K, et al. The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat Med. 2008;14(7):748–755. doi:10.1038/nm1763
   PubMed Web of Science ®Google Scholar
• Ostendorf L, Burns M, Durek P, et al. Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2020;383(12):1149–1155. doi:10.1056/NEJMoa2023325
   PubMed Web of Science ®Google Scholar
• Alexander T, Sarfert R, Klotsche J, et al. The proteasome inhibitor bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus. Ann Rheum Dis. 2015;74(7):1474–1478. doi:10.1136/annrheumdis-2014-206016
   PubMed Web of Science ®Google Scholar
• Faul C, Donnelly M, Merscher-Gomez S, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 2008;14(9):931–938. doi:10.1038/nm.1857
   PubMed Web of Science ®Google Scholar
• Jayne D, Rovin B, Mysler EF, et al. Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Ann Rheum Dis. 2022;81(4):496–506. doi:10.1136/annrheumdis-2021-221478
   PubMed Web of Science ®Google Scholar
• Steiger S, Anders H-J. Interferon blockade in lupus: effects on antiviral immunity. Nat Rev Nephrol. 2022;18:415–416. doi:10.1038/s41581-022-00581-0
   PubMed Web of Science ®Google Scholar
• Khamashta M, Merrill JT, Werth VP, et al. Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016;75(11):1909–1916. doi:10.1136/annrheumdis-2015-208562
   PubMed Web of Science ®Google Scholar
• Kalunian KC, Merrill JT, Maciuca R, et al. A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis. 2016;75(1):196–202. doi:10.1136/annrheumdis-2014-206090
   PubMed Web of Science ®Google Scholar
• Wallace DJ, Furie RA, Tanaka Y, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2018;392(10143):222–231. doi:10.1016/S0140-6736(18)31363-1
   PubMed Web of Science ®Google Scholar
• Hasni SA, Gupta S, Davis M, et al. Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus. Nat Commun. 2021;12(1):3391. doi:10.1038/s41467-021-23361-z
   PubMed Web of Science ®Google Scholar
• Furumoto Y, Smith CK, Blanco L, et al. Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction. Arthritis Rheumatol. 2017;69(1):148–160. doi:10.1002/art.39818
   PubMed Web of Science ®Google Scholar
• Baker M, Chaichian Y, Genovese M, et al. Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. RMD Open. 2020;6(3):e001490. doi:10.1136/rmdopen-2020-001490
   PubMed Web of Science ®Google Scholar
• Bao L, Cunningham PN, Quigg RJ. Complement in Lupus Nephritis: new Perspectives. Kidney Dis. 2015;1:91–99. doi:10.1159/000431278
   Web of Science ®Google Scholar
• Li NL, Birmingham DJ, Rovin BH. Expanding the Role of Complement Therapies: the Case for Lupus Nephritis. J Clin Med. 2021;10:626. doi:10.3390/jcm10040626
   PubMed Web of Science ®Google Scholar
• Martin M, Blom AM. Complement in removal of the dead - balancing inflammation. Immunol Rev. 2016;274:218–232. doi:10.1111/imr.12462
   PubMed Web of Science ®Google Scholar
• Birmingham DJ, Hebert LA. CR1 and CR1-like: the primate immune adherence receptors. Immunol Rev. 2001;180:100–111. doi:10.1034/j.1600-065X.2001.1800109.x
   PubMed Web of Science ®Google Scholar
• Birmingham DJ, Gavit KF, McCarty SM, et al. Consumption of erythrocyte CR1 (CD35) is associated with protection against systemic lupus erythematosus renal flare. Clin Exp Immunol. 2006;143(2):274–280. doi:10.1111/j.1365-2249.2005.02983.x
   PubMed Web of Science ®Google Scholar
• 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. Ann Rheum Dis. 2020;79(1):141–149. doi:10.1136/annrheumdis-2019-215396
   PubMed Web of Science ®Google Scholar
• Koga T, Ichinose K, Kawakami A, Tsokos GC. The role of IL-17 in systemic lupus erythematosus and its potential as a therapeutic target. Expert Rev Clin Immunol. 2019;15:629–637. doi:10.1080/1744666X.2019.1593141
   PubMed Web of Science ®Google Scholar
• Morel T, Cano S, Bartlett SJ, et al. The FATIGUE-PRO: a new patient-reported outcome instrument to quantify fatigue in patients affected by systemic lupus erythematosus. Rheumatology. 2022;61(8):3329–3340. doi:10.1093/rheumatology/keab920
   PubMed Web of Science ®Google Scholar
• Oaks Z, Winans T, Huang N, Banki K, Perl A. Activation of the mechanistic target of rapamycin in SLE: explosion of evidence in the last five years. Curr Rheumatol Rep. 2016;18:73. doi:10.1007/s11926-016-0622-8
   PubMed Web of Science ®Google Scholar
• Mao Z, Tan Y, Tao J, et al. Renal mTORC1 activation is associated with disease activity and prognosis in lupus nephritis. Rheumatology. 2022;61(9):3830–3840. doi:10.1093/rheumatology/keac037
   PubMed Web of Science ®Google Scholar
• Lui SL, Yung S, Tsang R, et al. Rapamycin prevents the development of nephritis in lupus-prone NZB/W F 1 mice. Lupus. 2008;17(4):305–313. doi:10.1177/0961203307088289
   PubMed Web of Science ®Google Scholar
• Zhang C, Chan CY, Cheung K, et al. Effect of mycophenolate and rapamycin on renal fibrosis in lupus nephritis. Clin Sci. 2019;133(15):1721–1744. doi:10.1042/CS20190536
   PubMed Web of Science ®Google Scholar
• Lai Z-W, 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. Lancet. 2018;391(10126):1186–1196. doi:10.1016/S0140-6736(18)30485-9
   PubMed Web of Science ®Google Scholar
• Dutta D, Barr VA, Akpan I, et al. Recruitment of calcineurin to the TCR positively regulates T cell activation. Nat Immunol. 2017;18(2):196–204. doi:10.1038/ni.3640
   PubMed Web of Science ®Google Scholar
• Sin FE, Isenberg D. An evaluation of voclosporin for the treatment of lupus nephritis. Expert Opin Pharmacother. 2018;19:1613–1621. doi:10.1080/14656566.2018.1516751
   PubMed Web of Science ®Google Scholar
• Rovin BH, Teng YKO, Ginzler EM, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (Aurora 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021;397(10289):2070–2080. doi:10.1016/S0140-6736(21)00578-X
   PubMed Web of Science ®Google Scholar
• Bao H, Liu Z-H, Xie H-L, et al. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol. 2008;19(10):2001–2010. doi:10.1681/ASN.2007121272
   PubMed Web of Science ®Google Scholar
• Liu Z, Zhang H, Liu Z, et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med. 2015;162(1):18–26. doi:10.7326/M14-1030
   PubMed Web of Science ®Google Scholar
• Zhang H, Liu Z, Zhou M, et al. Multitarget therapy for maintenance treatment of lupus nephritis. J Am Soc Nephrol. 2017;28(12):3671–3678. doi:10.1681/ASN.2017030263
   PubMed Web of Science ®Google Scholar
• Chen W, Tang X, Liu Q, et al. Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: a multicenter randomized clinical trial. Am J Kidney Dis. 2011;57(2):235–244. doi:10.1053/j.ajkd.2010.08.036
   PubMed Web of Science ®Google Scholar
• Li X, Ren H, Zhang Q, et al. Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis. Nephrol Dial Transplant. 2012;27(4):1467–1472. doi:10.1093/ndt/gfr484
   PubMed Web of Science ®Google Scholar
• Mok CC, Ying KY, Yim CW, et al. Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up. Ann Rheum Dis. 2016;75(1):30–36. doi:10.1136/annrheumdis-2014-206456
   PubMed Web of Science ®Google Scholar
• Mok CC, Ho LY, Ying SKY, et al. Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis. Ann Rheum Dis. 2020;79(8):1070–1076. doi:10.1136/annrheumdis-2020-217178
   PubMed Web of Science ®Google Scholar
• Zheng Z, Zhang H, Peng X, et al. Effect of tacrolimus vs intravenous cyclophosphamide on complete or partial response in patients with lupus nephritis: a randomized clinical trial. JAMA Netw Open. 2022;5(3):e224492. doi:10.1001/jamanetworkopen.2022.4492
   PubMed Web of Science ®Google Scholar
• Choi C-B, Won S, Bae S-C. Outcomes of multitarget therapy using mycophenolate mofetil and tacrolimus for refractory or relapsing lupus nephritis. Lupus. 2018;27:1007–1011. doi:10.1177/0961203318758505
   PubMed Web of Science ®Google Scholar
• Yap DYH, Li PH, Tang C, et al. Long-term results of triple immunosuppression with tacrolimus added to mycophenolate and corticosteroids in the treatment of lupus nephritis. Kidney Int Rep. 2022;7(3):516–525. doi:10.1016/j.ekir.2021.12.005
   PubMed Web of Science ®Google Scholar
• Austin HA, Illei GG, Braun MJ, Balow JE. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol. 2009;20:901–911. doi:10.1681/ASN.2008060665
   PubMed Web of Science ®Google Scholar
• Zavada J, Pešickova SS, Ryšava R, et al. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study. Lupus. 2010;19(11):1281–1289. doi:10.1177/0961203310371155
   PubMed Web of Science ®Google Scholar