Autoreactive B cells are one of the key immune cells that have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). In addition to the production of harmful auto-antibodies (auto-Abs), B cells prime autoreactive T cells as antigen-presenting cells and secrete a wide range of pro-inflammatory cytokines that have both autocrine and paracrine effects. Agents that modulate B cells may therefore be of potential therapeutic value. Current strategies include targeting B-cell surface antigens, cytokines that promote B-cell growth and functions, and B- and T-cell interactions. In this article, we review the role of B cells in SLE in animal and human studies, and we examine previous reports that support B-cell modulation as a promising strategy for the treatment of this condition. In addition, we present an update on the clinical trials that have evaluated the therapeutic efficacy and safety of agents that antagonize CD20, CD22 and B-lymphocyte stimulator (BLyS) in human SLE. While the results of many of these studies remain inconclusive, belimumab, a human monoclonal antibody against BLyS, has shown promise and has recently been approved by the US Food and Drug Administration as an indicated therapy for patients with mild to moderate SLE. Undoubtedly, advances in B-cell immunology will continue to lead us to a better understanding of SLE pathogenesis and the development of novel specific therapies that target B cells.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Characterization of the mechanism of action of lanraplenib, a novel spleen tyrosine kinase inhibitor, in models of lupus nephritis
BMC Rheumatology Open Access 30 March 2021
Clinical Epigenetics Open Access 02 August 2017
Inflammation and Regeneration Open Access 21 July 2016
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Lahita RG . The Clinical Presentation Systemic lupus erythematosus. In: Tsokos G, Buyon JP, Koike T, Lahita RG (eds) Systemic Lupus Erythematosus. 5th ed. San Diego, Elsevier Academic Press, 2011: 525–539 .
Mok CC, Lau CS . Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003; 56: 481–490.
Rahman A, Isenberg DA . Systemic lupus erythematosus. N Engl J Med 2008; 358: 929–939.
Shlomchik MJ, Craft JE, Mamula MJ . From T to B and back again: positive feedback in systemic autoimmune disease. Nat Rev Immunol 2001; 1: 147–153.
Sanz I, Lee FE . B cells as therapeutic targets in SLE. Nat Rev Rheumatol 2010; 6: 326–337.
Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349: 1526–1533.
Reichlin M . Ribosomal P antibodies and CNS lupus. Lupus 2003; 12: 916–918.
Alba P, Bento L, Cuadrado MJ, Karim Y, Tungekar MF, Abbs I et al. Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis. Ann Rheum Dis 2003; 62: 556–560.
Forger F, Matthias T, Oppermann M, Becker H, Helmke K . Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis. Lupus 2004; 13: 36–44.
Cortes-Hernandez J, Ordi-Ros J, Labrador M, Bujan S, Balada E, Segarra A et al. Antihistone and anti-double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus. Am J Med 2004; 116: 165–173.
Jacob L, Lety MA, Louvard D, Bach JF . Binding of a monoclonal anti-DNA autoantibody to identical protein(s) present at the surface of several human cell types involved in lupus pathogenesis. J Clin Invest 1985; 75: 315–317.
Zhao Z, Weinstein E, Tuzova M, Davidson A, Mundel P, Marambio P et al. Cross-reactivity of human lupus anti-DNA antibodies with alpha-actinin and nephritogenic potential. Arthritis Rheum 2005; 52: 522–530.
Faaber P, Rijke TP, van de Putte LB, Capel PJ, Berden JH . Cross-reactivity of human and murine anti-DNA antibodies with heparan sulfate. The major glycosaminoglycan in glomerular basement membranes. J Clin Invest 1986; 77: 1824–1830.
Ehrenstein MR, Katz DR, Griffiths MH, Papadaki L, Winkler TH, Kalden JR et al. Human IgG anti-DNA antibodies deposit in kidneys and induce proteinuria in SCID mice. Kidney Int 1995; 48: 705–711.
Vlahakos D, Foster MH, Ucci AA, Barrett KJ, Datta SK, Madaio MP . Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo. J Am Soc Nephrol 1992; 2: 1345–1354.
O'Neill SK, Shlomchik MJ, Glant TT, Cao Y, Doodes PD, Finnegan A . Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis. J Immunol 2005; 174: 3781–3788.
Shlomchik MJ, Madaio MP, Ni D, Trounstein M, Huszar D . The role of B cells in lpr/lpr-induced autoimmunity. J Exp Med 1994; 180: 1295–1306.
Chan O, Shlomchik MJ . A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice. J Immunol 1998; 160: 51–59.
Chan OT, Hannum LG, Haberman AM, Madaio MP, Shlomchik MJ . A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J Exp Med 1999; 189: 1639–1648.
Steinmetz OM, Velden J, Kneissler U, Marx M, Klein A, Helmchen U et al. Analysis and classification of B-cell infiltrates in lupus and ANCA-associated nephritis. Kidney Int 2008; 74: 448–457.
Mamula MJ, Fatenejad S, Craft J . B cells process and present lupus autoantigens that initiate autoimmune T cell responses. J Immunol 1994; 152: 1453–1461.
Pistoia V . Production of cytokines by human B cells in health and disease. Immunol Today 1997; 18: 343–350.
Duddy ME, Alter A, Bar-Or A . Distinct profiles of human B cell effector cytokines: a role in immune regulation? J Immunol 2004; 172: 3422–3427.
Ronnblom L, Elkon KB . Cytokines as therapeutic targets in SLE. Nat Rev Rheumatol 2010; 6: 339–347.
Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IA, Dolman KM et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest 2010; 120: 214–222.
Oflazoglu E, Audoly LP . Evolution of anti-CD20 monoclonal antibody therapeutics in oncology. MAbs 2010; 2: 14–19.
Looney RJ, Anolik J, Sanz I . Treatment of SLE with anti-CD20 monoclonal antibody. Curr Dir Autoimmun 2005; 8: 193–205.
Deng Y, Tsao BP . Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat Rev Rheumatol 2010; 6: 683–692.
Anolik JH, Campbell D, Felgar RE, Young F, Sanz I, Rosenblatt J et al. The relationship of FcgammaRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum 2003; 48: 455–459.
Albert D, Dunham J, Khan S, Stansberry J, Kolasinski S, Tsai D et al. Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus. Ann Rheum Dis 2008; 67: 1724–1731.
Robak E, Robak T . Monoclonal antibodies in the treatment of systemic lupus erythematosus. Curr Drug Targets 2009; 10: 26–37.
Dorner T, Goldenberg DM . Targeting CD22 as a strategy for treating systemic autoimmune diseases. Ther Clin Risk Manag 2007; 3: 953–959.
Tedder TF, Poe JC, Haas KM . CD22: a multifunctional receptor that regulates B lymphocyte survival and signal transduction. Adv Immunol 2005; 88: 1–50.
Fujimoto M, Poe JC, Hasegawa M, Tedder TF . CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification. Immunol Res 2000; 22: 281–298.
Jacobi AM, Goldenberg DM, Hiepe F, Radbruch A, Burmester GR, Dorner T . Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls. Ann Rheum Dis 2008; 67: 450–457.
Daridon C, Blassfeld D, Reiter K, Mei HE, Giesecke C, Goldenberg DM et al. Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus. Arthritis Res Ther 2010; 12: R204.
Wayne AS, Kreitman RJ, Findley HW, Lew G, Delbrook C, Steinberg SM et al. Anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-positive hematologic malignancies of childhood: preclinical studies and phase I clinical trial. Clin Cancer Res 2010; 16: 1894–1903.
Blanc V, Bousseau A, Caron A, Carrez C, Lutz RJ, Lambert JM . SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies. Clin Cancer Res 2011; 17: 6448–6458.
Mauri C, Bosma A . Immune regulatory function of B cells. Annu Rev Immunol 2012; 30: 221–241.
Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K et al. Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol 2010; 184: 4801–4809.
Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR et al. CD19+CD24hiCD38hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity 2010; 32: 129–140.
Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science 1999; 285: 260–263.
Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med 1999; 189: 1747–1756.
Mackay F, Schneider P, Rennert P, Browning J . BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol 2003; 21: 231–264.
Crowley JE, Treml LS, Stadanlick JE, Carpenter E, Cancro MP . Homeostatic niche specification among naive and activated B cells: a growing role for the BLyS family of receptors and ligands. Semin Immunol 2005; 17: 193–199.
Cheema GS, Roschke V, Hilbert DM, Stohl W . Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum 2001; 44: 1313–1319.
Mariette X, Roux S, Zhang J, Bengoufa D, Lavie F, Zhou T et al. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjogren's syndrome. Ann Rheum Dis 2003; 62: 168–171.
Zhang J, Roschke V, Baker KP, Wang Z, Alarcon GS, Fessler BJ et al. Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol 2001; 166: 6–10.
Collins CE, Gavin AL, Migone TS, Hilbert DM, Nemazee D, Stohl W . B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels. Arthritis Res Ther 2006; 8: R6.
Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J et al. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum 2008; 58: 2453–2459.
Chu VT, Enghard P, Schurer S, Steinhauser G, Rudolph B, Riemekasten G et al. Systemic activation of the immune system induces aberrant BAFF and APRIL expression in B cells in patients with systemic lupus erythematosus. Arthritis Rheum 2009; 60: 2083–2093.
Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med 1999; 190: 1697–1710.
Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 2000; 404: 995–999.
Groom JR, Fletcher CA, Walters SN, Grey ST, Watt SV, Sweet MJ et al. BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J Exp Med 2007; 204: 1959–1971.
Jacob CO, Pricop L, Putterman C, Koss MN, Liu Y, Kollaros M et al. Paucity of clinical disease despite serological autoimmunity and kidney pathology in lupus-prone New Zealand mixed 2328 mice deficient in BAFF. J Immunol 2006; 177: 2671–2680.
Jacob CO, Guo S, Jacob N, Pawar RD, Putterman C, Quinn WJ 3rd et al. Dispensability of APRIL to the development of systemic lupus erythematosus in NZM 2328 mice. Arthritis Rheum 2012; 64: 1610–1619.
Ramanujam M, Wang X, Huang W, Liu Z, Schiffer L, Tao H et al. Similarities and differences between selective and nonselective BAFF blockade in murine SLE. J Clin Invest 2006; 116: 724–734.
Naka T, Nishimoto N, Kishimoto T . The paradigm of IL-6: from basic science to medicine. Arthritis Res 2002; 4 Suppl 3: S233–242.
Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 1986; 324: 73–76.
Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR . Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. J Immunol 1991; 147: 117–123.
Grondal G, Gunnarsson I, Ronnelid J, Rogberg S, Klareskog L, Lundberg I . Cytokine production, serum levels and disease activity in systemic lupus erythematosus. Clin Exp Rheumatol 2000; 18: 565–570.
Esposito P, Balletta MM, Procino A, Postiglione L, Memoli B . Interleukin-6 release from peripheral mononuclear cells is associated to disease activity and treatment response in patients with lupus nephritis. Lupus 2009; 18: 1329–1330.
Hagiwara E, Gourley MF, Lee S, Klinman DK . Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10:interferon-gamma-secreting cells in the peripheral blood. Arthritis Rheum 1996; 39: 379–385.
Takeno M, Nagafuchi H, Kaneko S, Wakisaka S, Oneda K, Takeba Y et al. Autoreactive T cell clones from patients with systemic lupus erythematosus support polyclonal autoantibody production. J Immunol 1997; 158: 3529–3538.
Kitani A, Hara M, Hirose T, Harigai M, Suzuki K, Kawakami M et al. Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression. Clin Exp Immunol 1992; 88: 75–83.
Nagafuchi H, Suzuki N, Mizushima Y, Sakane T . Constitutive expression of IL-6 receptors and their role in the excessive B cell function in patients with systemic lupus erythematosus. J Immunol 1993; 151: 6525–6534.
Mihara M, Fukui H, Koishihara Y, Saito M, Ohsugi Y . Immunologic abnormality in NZB/W F1 mice. Thymus-independent expansion of B cells responding to interleukin-6. Clin Exp Immunol 1990; 82: 533–537.
Alarcon-Riquelme ME, Moller G, Fernandez C . Age-dependent responsiveness to interleukin-6 in B lymphocytes from a systemic lupus erythematosus-prone (NZB×NZW)F1 hybrid. Clin Immunol Immunopathol 1992; 62: 264–269.
Finck BK, Chan B, Wofsy D . Interleukin 6 promotes murine lupus in NZB/NZW F1 mice. J Clin Invest 1994; 94: 585–591.
Liang B, Gardner DB, Griswold DE, Bugelski PJ, Song XY . Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus. Immunology 2006; 119: 296–305.
Kimura A, Kishimoto T . IL-6: regulator of Treg/Th17 balance. Eur J Immunol 2010; 40: 1830–1835.
Korn T, Bettelli E, Oukka M, Kuchroo VK . IL-17 and Th17 Cells. Annu Rev Immunol 2009; 27: 485–517.
Wan S, Xia C, Morel L . IL-6 produced by dendritic cells from lupus-prone mice inhibits CD4+CD25+ T cell regulatory functions. J Immunol 2007; 178: 271–279.
Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ . Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev 2009; 229: 152–172.
Foy TM, Durie FH, Noelle RJ . The expansive role of CD40 and its ligand, gp39, in immunity. Semin Immunol 1994; 6: 259–266.
Desai-Mehta A, Lu L, Ramsey-Goldman R, Datta SK . Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production. J Clin Invest 1996; 97: 2063–2073.
Koshy M, Berger D, Crow MK . Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes. J Clin Invest 1996; 98: 826–837.
Vakkalanka RK, Woo C, Kirou KA, Koshy M, Berger D, Crow MK . Elevated levels and functional capacity of soluble CD40 ligand in systemic lupus erythematosus sera. Arthritis Rheum 1999; 42: 871–881.
Kato K, Santana-Sahagun E, Rassenti LZ, Weisman MH, Tamura N, Kobayashi S et al. The soluble CD40 ligand sCD154 in systemic lupus erythematosus. J Clin Invest 1999; 104: s947–955.
Mohan C, Shi Y, Laman JD, Datta SK . Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis. J Immunol 1995; 154: 1470–1480.
Blossom S, Chu EB, Weigle WO, Gilbert KM . CD40 ligand expressed on B cells in the BXSB mouse model of systemic lupus erythematosus. J Immunol 1997; 159: 4580–4586.
Higuchi T, Aiba Y, Nomura T, Matsuda J, Mochida K, Suzuki M et al. Cutting Edge: Ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease. J Immunol 2002; 168: 9–12.
Early GS, Zhao W, Burns CM . Anti-CD40 ligand antibody treatment prevents the development of lupus-like nephritis in a subset of New Zealand black×New Zealand white mice. Response correlates with the absence of an anti-antibody response. J Immunol 1996; 157: 3159–3164.
Kalled SL, Cutler AH, Datta SK, Thomas DW . Anti-CD40 ligand antibody treatment of SNF1 mice with established nephritis: preservation of kidney function. J Immunol 1998; 160: 2158–2165.
Chambers CA, Kuhns MS, Egen JG, Allison JP . CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 2001; 19: 565–594.
Salomon B, Bluestone JA . Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 2001; 19: 225–252.
Davidson A, Diamond B, Wofsy D, Daikh D . Block and tackle: CTLA4Ig takes on lupus. Lupus 2005; 14: 197–203.
Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC 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.
Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J 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: 1215–1226.
Vigna-Perez M, Hernandez-Castro B, Paredes-Saharopulos O, Portales-Perez D, Baranda L, Abud-Mendoza C et al. Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther 2006; 8: R83.
Melander C, Sallee M, Trolliet P, Candon S, Belenfant X, Daugas E et al. Rituximab in severe lupus nephritis: early B-cell depletion affects long-term renal outcome. Clin J Am Soc Nephrol 2009; 4: 579–587.
Terrier B, Amoura Z, Ravaud P, Hachulla E, Jouenne R, Combe B et al. Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French AutoImmunity and Rituximab registry. Arthritis Rheum 2010; 62: 2458–2466.
Garcia-Carrasco M, Mendoza-Pinto C, Sandoval-Cruz M, Soto-Vega E, Beltran-Castillo A, Jimenez-Hernandez M et al. Anti-CD20 therapy in patients with refractory systemic lupus erythematosus: a longitudinal analysis of 52 Hispanic patients. Lupus 2010; 19: 213–219.
Ramos-Casals M, Soto MJ, Cuadrado MJ, Khamashta MA . Rituximab in systemic lupus erythematosus: A systematic review of off-label use in 188 cases. Lupus 2009; 18: 767–776.
Narshi CB, Haider S, Ford CM, Isenberg DA, Giles IP . Rituximab as early therapy for pulmonary haemorrhage in systemic lupus erythematosus. Rheumatology (Oxford) 2010; 49: 392–394.
Pinto LF, Candia L, Garcia P, Marin JI, Pachon I, Espinoza LR et al. Effective treatment of refractory pulmonary hemorrhage with monoclonal anti-CD20 antibody (rituximab). Respiration 2009; 78: 106–109.
Abud-Mendoza C, Moreno-Valdes R, Cuevas-Orta E, Borjas A, Aranda F, Irazoque F et al. Treating severe systemic lupus erythematosus with rituximab. An open study. Reumatol Clin 2009; 5: 147–152.
Mysler E, Spindler AJ, Guzman R, Bijl M, Jayne D, Furie RA et al. Efficacy and safety of ocrelizumab, a humanized antiCD20 antibody, in patients with active proliferative lupus nephritis (LN): results from the randomized, double-blind phase III BELONG study. Arthritis Rheum 2010; 62( Suppl 10): 1455.
Petri M, Hobbs K, Gordon C, Strand V, Wallace DJ, Kelley L et al. Randomized controlled trials of epratuzumab (anti-CD22 mAb targeting B-cells) reveal clinically meaningful improvements in patients with moderate/severe SLE flares. Annals of the Rheumatic diseases. Ann Rheum Dis 2008; 67( Suppl II): 53.
Wallace DJ, Hobbs K, Houssiau F, Strand V, Tak P, Wegener W et al. Randomized controlled trials of epratuzumab (anti-CD22 mAb targeting B-cells) reveal clinically meaningful reductions in corticosteroid use with favorable safety profile in moderate and severe flaring SLE patients. Ann Rheum Dis 2008; 67( Suppl II): 212.
Traczewski P, Rudnicka L . Treatment of systemic lupus erythematosus with epratuzumab. Br J Clin Pharmacol 2011; 71: 175–182.
Strand V, Kalunian K, Coteur G, Barry A, Keininger D, Wegener W et al. Randomized controlled trials of epratuzumab (anti-CD22 mAb targeting B-cells) show meaningful improvements in health related quality of life in SLE patients with high disease activity and low baseline self-report measures. Ann Rheum Dis 2008; 67( Suppl II): 212.
Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum 2009; 61: 1168–1178.
Petri M, Furie R, Merrill J, Wallace D, Stohl W, Chatham W, et al. Six-year experience with belimumab in patients with SLE [Abstract]. In: European League Against Rheumatism Meeting. London, UK, 2011.
Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377: 721–731.
Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzova D et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum 2011; 63: 3918–3930.
Manzi S, Sanchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis 2012; 71: 1833–1838.
van Vollenhoven RF, Petri MA, Cervera R, Roth DA, Ji BN, Kleoudis CS et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis 2012; 71: 1343–1349.
Chan VS, Nie YJ, Shen N, Yan S, Mok MY, Lau CS . Distinct roles of myeloid and plasmacytoid dendritic cells in systemic lupus erythematosus. Autoimmun Rev 2012; 11: 890–897.
Merrill JT, Wallace DJ, Petri M, Kirou KA, Yao Y, White WI et al. Safety profile and clinical activity of sifalimumab, a fully human anti-interferon alpha monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study. Ann Rheum Dis 2011; 70: 1905–1913.
Jacobi AM, Reiter K, Mackay M, Aranow C, Hiepe F, Radbruch A et al. Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: delineation by expression of CD27, IgD, and CD95. Arthritis Rheum 2008; 58: 1762–1773.
About this article
Cite this article
Chan, VF., Tsang, HL., Tam, RY. et al. B-cell-targeted therapies in systemic lupus erythematosus. Cell Mol Immunol 10, 133–142 (2013). https://doi.org/10.1038/cmi.2012.64
- Systemic lupus erythematosus, B-cell, autoimmunity, therapy
This article is cited by
Drug Delivery and Translational Research (2023)
Low dosage use of cyclophosphamide improves the survival of patients with systemic lupus erythematosus
Clinical Rheumatology (2022)
Characterization of the mechanism of action of lanraplenib, a novel spleen tyrosine kinase inhibitor, in models of lupus nephritis
BMC Rheumatology (2021)
Nature Reviews Rheumatology (2019)
Clinical Epigenetics (2017)