Skip to main content
Erschienen in: Seminars in Immunopathology 3/2014

01.05.2014 | Review

Rationale for B cell targeting in SLE

verfasst von: Iñaki Sanz

Erschienen in: Seminars in Immunopathology | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

B cells are central pathogenic players in systemic lupus erythematosus and multiple other autoimmune diseases through antibody production as well as antibody independent function. At the same time, B cells are known to play important regulatory functions that may protect against autoimmune manifestations. Yet, the functional role of different B cell populations and their contribution to disease remain to be understood. The advent of agents that specifically target B cells, in particular anti-CD20 and ant-BLyS antibodies, have demonstrated the efficacy of this approach for the treatment of human autoimmunity. The analysis of patients treated with these and other B cell agents provides a unique opportunity to understand the correlates of clinical response and the significance of different B cell subsets. Here, we discuss this information and how it could be used to better understand SLE and improve the rational design of B cell-directed therapies in this disease.
Literatur
1.
Zurück zum Zitat Chan AC (2011) B cell immunotherapy in autoimmunity—2010 update. Mol Immunol 48(11):1344–1347PubMedCrossRef Chan AC (2011) B cell immunotherapy in autoimmunity—2010 update. Mol Immunol 48(11):1344–1347PubMedCrossRef
2.
Zurück zum Zitat Manjarrez-Orduno N, Quach TD, Sanz I (2009) B cells and immunological tolerance. J Invest Dermatol 129(2):278–288PubMedCrossRef Manjarrez-Orduno N, Quach TD, Sanz I (2009) B cells and immunological tolerance. J Invest Dermatol 129(2):278–288PubMedCrossRef
3.
Zurück zum Zitat Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350:2572–2581PubMedCrossRef Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350:2572–2581PubMedCrossRef
4.
Zurück zum Zitat Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363(3):221–232. doi:10.1056/NEJMoa0909905 PubMedCentralPubMedCrossRef Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363(3):221–232. doi:10.​1056/​NEJMoa0909905 PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Merrill JT, Buyon JP, Furie RA, Latinis KM, Gordon C, Hsieh H-J, Brunetta PG (2011) Assessment of flares in lupus patients enrolled in a phase II/III study of rituximab (EXPLORER). Lupus. doi:10.1177/0961203310395802 Merrill JT, Buyon JP, Furie RA, Latinis KM, Gordon C, Hsieh H-J, Brunetta PG (2011) Assessment of flares in lupus patients enrolled in a phase II/III study of rituximab (EXPLORER). Lupus. doi:10.​1177/​0961203310395802​
7.
Zurück zum Zitat Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G, Group LI (2012) Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum 64(4):1215–1226. doi:10.1002/art.34359 PubMedCrossRef Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G, Group LI (2012) Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum 64(4):1215–1226. doi:10.​1002/​art.​34359 PubMedCrossRef
10.
Zurück zum Zitat Sanz I (2014) Pharmacological effects and mechanisms of action of agents blocking B cells. In: Bosch X, Ramos-Casals M, Khamashta MA (eds) Drugs targeting B-cells in autoimmune diseases. Milestones in Drug Therapy. Springer Basel, pp 37–64. doi:10.1007/978-3-0348-0706-7_3 Sanz I (2014) Pharmacological effects and mechanisms of action of agents blocking B cells. In: Bosch X, Ramos-Casals M, Khamashta MA (eds) Drugs targeting B-cells in autoimmune diseases. Milestones in Drug Therapy. Springer Basel, pp 37–64. doi:10.​1007/​978-3-0348-0706-7_​3
11.
Zurück zum Zitat Hiepe F, Dorner T, Hauser AE, Hoyer BF, Mei H, Radbruch A (2011) Long-lived autoreactive plasma cells drive persistent autoimmune inflammation. Nat Rev Rheumatol advance online publication Hiepe F, Dorner T, Hauser AE, Hoyer BF, Mei H, Radbruch A (2011) Long-lived autoreactive plasma cells drive persistent autoimmune inflammation. Nat Rev Rheumatol advance online publication
13.
Zurück zum Zitat Fillatreau S, Gray D, Anderton SM (2008) Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol 8:391–397PubMedCrossRef Fillatreau S, Gray D, Anderton SM (2008) Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol 8:391–397PubMedCrossRef
14.
Zurück zum Zitat Zhong X, Gao W, Degauque N, Bai C, Lu Y, Kenny J, Oukka M, Strom TB, Rothstein TL (2007) Reciprocal generation of Th1/Th17 and Treg by B1 and B2 B cells. Eur J Immunol 9999(9999):NA Zhong X, Gao W, Degauque N, Bai C, Lu Y, Kenny J, Oukka M, Strom TB, Rothstein TL (2007) Reciprocal generation of Th1/Th17 and Treg by B1 and B2 B cells. Eur J Immunol 9999(9999):NA
15.
Zurück zum Zitat Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM, Johnson LL, Swain SL, Lund FE (2000) Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1(6):475–482PubMedCrossRef Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM, Johnson LL, Swain SL, Lund FE (2000) Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1(6):475–482PubMedCrossRef
16.
Zurück zum Zitat Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein MR, Isenberg DA, Mauri C (2013) CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med 5(173):173ra123. doi:10.1126/scitranslmed.3005407 CrossRef Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein MR, Isenberg DA, Mauri C (2013) CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med 5(173):173ra123. doi:10.​1126/​scitranslmed.​3005407 CrossRef
17.
Zurück zum Zitat Chen X, Jensen PE (2007) Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3+ CD4 T cells. J Immunol 179(4):2046–2050PubMedCrossRef Chen X, Jensen PE (2007) Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3+ CD4 T cells. J Immunol 179(4):2046–2050PubMedCrossRef
18.
Zurück zum Zitat Olson TS, Bamias G, Naganuma M, Rivera-Nieves J, Burcin TL, Ross W, Morris MA, Pizarro TT, Ernst PB, Cominelli F, Ley K (2004) Expanded B cell population blocks regulatory T cells and exacerbates ileitis in a murine model of Crohn disease. J Clin Invest 114(3):389–398. doi:10.1172/jci200420855 PubMedCentralPubMedCrossRef Olson TS, Bamias G, Naganuma M, Rivera-Nieves J, Burcin TL, Ross W, Morris MA, Pizarro TT, Ernst PB, Cominelli F, Ley K (2004) Expanded B cell population blocks regulatory T cells and exacerbates ileitis in a murine model of Crohn disease. J Clin Invest 114(3):389–398. doi:10.​1172/​jci200420855 PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Yanaba K, Bouaziz J-D, Haas KM, Poe JC, Fujimoto M, Tedder TF (2008) A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28(5):639–650PubMedCrossRef Yanaba K, Bouaziz J-D, Haas KM, Poe JC, Fujimoto M, Tedder TF (2008) A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28(5):639–650PubMedCrossRef
20.
Zurück zum Zitat Iwata Y, Matsushita T, Horikawa M, DiLillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, Hall RP, St Clair EW, Tedder TF (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117(2):530–541. doi:10.1182/blood-2010-07-294249 PubMedCentralPubMedCrossRef Iwata Y, Matsushita T, Horikawa M, DiLillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, Hall RP, St Clair EW, Tedder TF (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117(2):530–541. doi:10.​1182/​blood-2010-07-294249 PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, Mauri C (2010) CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity 32(1):129–140. doi:10.1016/j.immuni.2009.11.009 PubMedCrossRef Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, Mauri C (2010) CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity 32(1):129–140. doi:10.​1016/​j.​immuni.​2009.​11.​009 PubMedCrossRef
23.
Zurück zum Zitat Martin F, Chan AC (2006) B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol 24(1) Martin F, Chan AC (2006) B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol 24(1)
25.
Zurück zum Zitat Merrell KT, Benschop RJ, Gauld SB, Aviszus K, Decote-Ricardo D, Wysocki LJ, Cambier JC (2006) Identification of anergic B cells within a wild-type repertoire. Immunity 25(6):953–962PubMedCrossRef Merrell KT, Benschop RJ, Gauld SB, Aviszus K, Decote-Ricardo D, Wysocki LJ, Cambier JC (2006) Identification of anergic B cells within a wild-type repertoire. Immunity 25(6):953–962PubMedCrossRef
26.
Zurück zum Zitat Teague BN, Pan Y, Mudd PA, Nakken B, Zhang Q, Szodoray P, Kim-Howard X, Wilson PC, Farris AD (2007) Cutting edge: transitional T3 B cells do not give rise to mature b cells, have undergone selection, and are reduced in murine lupus. J Immunol 178(12):7511–7515PubMedCrossRef Teague BN, Pan Y, Mudd PA, Nakken B, Zhang Q, Szodoray P, Kim-Howard X, Wilson PC, Farris AD (2007) Cutting edge: transitional T3 B cells do not give rise to mature b cells, have undergone selection, and are reduced in murine lupus. J Immunol 178(12):7511–7515PubMedCrossRef
28.
Zurück zum Zitat Ettinger R, Sims GP, Robbins R, Withers D, Fischer RT, Grammer AC, Kuchen S, Lipsky PE (2007) IL-21 and BAFF/BLyS synergize in stimulating plasma cell differentiation from a unique population of human splenic memory B cells. J Immunol 178(5):2872–2882PubMedCrossRef Ettinger R, Sims GP, Robbins R, Withers D, Fischer RT, Grammer AC, Kuchen S, Lipsky PE (2007) IL-21 and BAFF/BLyS synergize in stimulating plasma cell differentiation from a unique population of human splenic memory B cells. J Immunol 178(5):2872–2882PubMedCrossRef
29.
30.
Zurück zum Zitat Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, Plebani A, Kumararatne DS, Bonnet D, Tournilhac O, Tchernia G, Steiniger B, Staudt LM, Casanova J-L, Reynaud C-A, Weill J-C (2004) Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a pre-diversified immunoglobulin repertoire. Blood:2004-2001-0346 Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, Plebani A, Kumararatne DS, Bonnet D, Tournilhac O, Tchernia G, Steiniger B, Staudt LM, Casanova J-L, Reynaud C-A, Weill J-C (2004) Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a pre-diversified immunoglobulin repertoire. Blood:2004-2001-0346
36.
Zurück zum Zitat Yurasov S, Wardemann H, Hammersen J, Tsuiji M, Meffre E, Pascual V, Nussenzweig MC (2005) Defective B cell tolerance checkpoints in systemic lupus erythematosus. J Exp Med 201(5):703–711PubMedCentralPubMedCrossRef Yurasov S, Wardemann H, Hammersen J, Tsuiji M, Meffre E, Pascual V, Nussenzweig MC (2005) Defective B cell tolerance checkpoints in systemic lupus erythematosus. J Exp Med 201(5):703–711PubMedCentralPubMedCrossRef
37.
38.
Zurück zum Zitat Lesley R, Xu Y, Kalled SL, Hess DM, Schwab SR, Shu HB, Cyster JG (2004) Reduced competitiveness of autoantigen-engaged b cells due to increased dependence on BAFF. Immunity 20(4):441–453PubMedCrossRef Lesley R, Xu Y, Kalled SL, Hess DM, Schwab SR, Shu HB, Cyster JG (2004) Reduced competitiveness of autoantigen-engaged b cells due to increased dependence on BAFF. Immunity 20(4):441–453PubMedCrossRef
39.
41.
Zurück zum Zitat Chan TD, Gatto D, Wood K, Camidge T, Basten A, Brink R (2009) Antigen affinity controls rapid T-dependent antibody production by driving the expansion rather than the differentiation or extrafollicular migration of early plasmablasts. J Immunol 183(5):3139–3149. doi:10.4049/jimmunol.0901690 PubMedCrossRef Chan TD, Gatto D, Wood K, Camidge T, Basten A, Brink R (2009) Antigen affinity controls rapid T-dependent antibody production by driving the expansion rather than the differentiation or extrafollicular migration of early plasmablasts. J Immunol 183(5):3139–3149. doi:10.​4049/​jimmunol.​0901690 PubMedCrossRef
44.
Zurück zum Zitat Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KGC, Dorner T, Hiepe F (2006) Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol 6(10):741–750PubMedCrossRef Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KGC, Dorner T, Hiepe F (2006) Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol 6(10):741–750PubMedCrossRef
46.
Zurück zum Zitat Kaji T, Ishige A, Hikida M, Taka J, Hijikata A, Kubo M, Nagashima T, Takahashi Y, Kurosaki T, Okada M, Ohara O, Rajewsky K, Takemori T (2012) Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. J Exp Med 209(11):2079–2097. doi:10.1084/jem.20120127 PubMedCentralPubMedCrossRef Kaji T, Ishige A, Hikida M, Taka J, Hijikata A, Kubo M, Nagashima T, Takahashi Y, Kurosaki T, Okada M, Ohara O, Rajewsky K, Takemori T (2012) Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. J Exp Med 209(11):2079–2097. doi:10.​1084/​jem.​20120127 PubMedCentralPubMedCrossRef
48.
Zurück zum Zitat Bernasconi NL, Onai N, Lanzavecchia A (2003) A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. Blood:2002-2011-3569 Bernasconi NL, Onai N, Lanzavecchia A (2003) A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. Blood:2002-2011-3569
49.
Zurück zum Zitat Bernasconi NL, Traggiai E, Lanzavecchia A (2002) Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298(5601):2199–2202PubMedCrossRef Bernasconi NL, Traggiai E, Lanzavecchia A (2002) Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298(5601):2199–2202PubMedCrossRef
50.
Zurück zum Zitat Calero I, Nieto JA, Sanz I (2010) B cell therapies for rheumatoid arthritis: beyond B cell depletion. Rheum Dis Clin N Am 36(2):325–343CrossRef Calero I, Nieto JA, Sanz I (2010) B cell therapies for rheumatoid arthritis: beyond B cell depletion. Rheum Dis Clin N Am 36(2):325–343CrossRef
51.
Zurück zum Zitat Calero I, Sanz I (2010) Targeting B cells for the treatment of SLE: the beginning of the end or the end of the beginning? Discov Med 10(54):416–424PubMed Calero I, Sanz I (2010) Targeting B cells for the treatment of SLE: the beginning of the end or the end of the beginning? Discov Med 10(54):416–424PubMed
57.
Zurück zum Zitat Qian Y, Wei C, Eun-Hyung Lee F, Campbell J, Halliley J, Lee JA, Cai J, Kong YM, Sadat E, Thomson E, Dunn P, Seegmiller AC, Karandikar NJ, Tipton CM, Mosmann T, Sanz I, Scheuermann RH (2010) Elucidation of seventeen human peripheral blood B-cell subsets and quantification of the tetanus response using a density-based method for the automated identification of cell populations in multidimensional flow cytometry data. Cytometry B Clin Cytom 78B(S1):S69–S82. doi:10.1002/cyto.b.20554 CrossRef Qian Y, Wei C, Eun-Hyung Lee F, Campbell J, Halliley J, Lee JA, Cai J, Kong YM, Sadat E, Thomson E, Dunn P, Seegmiller AC, Karandikar NJ, Tipton CM, Mosmann T, Sanz I, Scheuermann RH (2010) Elucidation of seventeen human peripheral blood B-cell subsets and quantification of the tetanus response using a density-based method for the automated identification of cell populations in multidimensional flow cytometry data. Cytometry B Clin Cytom 78B(S1):S69–S82. doi:10.​1002/​cyto.​b.​20554 CrossRef
58.
Zurück zum Zitat Palanichamy A, Bernard J, Owen T, Zheng B, Conley T, Quach T, Wei C, Looney J, Sanz I, Anolik JH (2008) Characterization of human late transitional B cells: implications for systemic lupus. Arthritis Rheum 58(9):S446 Palanichamy A, Bernard J, Owen T, Zheng B, Conley T, Quach T, Wei C, Looney J, Sanz I, Anolik JH (2008) Characterization of human late transitional B cells: implications for systemic lupus. Arthritis Rheum 58(9):S446
59.
Zurück zum Zitat Wei C, Anolik J, Cappione A, Zheng B, Pugh-Bernard A, Brooks J, Lee EH, Milner EC, Sanz I (2007) A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J Immunol 178(10):6624–6633PubMedCrossRef Wei C, Anolik J, Cappione A, Zheng B, Pugh-Bernard A, Brooks J, Lee EH, Milner EC, Sanz I (2007) A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J Immunol 178(10):6624–6633PubMedCrossRef
61.
Zurück zum Zitat Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, O’Shea MA, Roby G, Kottilil S, Arthos J, Proschan MA, Chun T-W, Fauci AS (2008) Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med 205(8):1797–1805. doi:10.1084/jem.20072683 PubMedCentralPubMedCrossRef Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, O’Shea MA, Roby G, Kottilil S, Arthos J, Proschan MA, Chun T-W, Fauci AS (2008) Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med 205(8):1797–1805. doi:10.​1084/​jem.​20072683 PubMedCentralPubMedCrossRef
62.
Zurück zum Zitat Berkowska MA, Driessen GJA, Bikos V, Grosserichter-Wagener C, Stamatopoulos K, Cerutti A, He B, Biermann K, Lange JF, van der Burg M, van Dongen JJM, van Zelm MC (2011) Human memory B cells originate from three distinct germinal center-dependent and -independent maturation pathways. Blood 118(8):2150–2158. doi:10.1182/blood-2011-04-345579 PubMedCentralPubMedCrossRef Berkowska MA, Driessen GJA, Bikos V, Grosserichter-Wagener C, Stamatopoulos K, Cerutti A, He B, Biermann K, Lange JF, van der Burg M, van Dongen JJM, van Zelm MC (2011) Human memory B cells originate from three distinct germinal center-dependent and -independent maturation pathways. Blood 118(8):2150–2158. doi:10.​1182/​blood-2011-04-345579 PubMedCentralPubMedCrossRef
63.
Zurück zum Zitat Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3(10):944–950PubMedCrossRef Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3(10):944–950PubMedCrossRef
66.
Zurück zum Zitat Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, Mauri C (2007) Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol 178(12):7868–7878PubMedCrossRef Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, Mauri C (2007) Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol 178(12):7868–7878PubMedCrossRef
67.
Zurück zum Zitat Duddy M, Niino M, Adatia F, Hebert S, Freedman M, Atkins H, Kim HJ, Bar-Or A (2007) Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol 178(10):6092–6099PubMedCrossRef Duddy M, Niino M, Adatia F, Hebert S, Freedman M, Atkins H, Kim HJ, Bar-Or A (2007) Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol 178(10):6092–6099PubMedCrossRef
68.
Zurück zum Zitat Tan EM (1989) Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 44:93–151PubMedCrossRef Tan EM (1989) Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 44:93–151PubMedCrossRef
69.
Zurück zum Zitat Jenks SA, Palmer EM, Marin EY, Hartson L, Chida AS, Richardson C, Sanz I (2013) 9G4+ autoantibodies are an important source of apoptotic cell reactivity associated with high levels of disease activity in systemic lupus erythematosus. Arthritis Rheum 65(12):3165–3175. doi:10.1002/art.38138 PubMedCrossRef Jenks SA, Palmer EM, Marin EY, Hartson L, Chida AS, Richardson C, Sanz I (2013) 9G4+ autoantibodies are an important source of apoptotic cell reactivity associated with high levels of disease activity in systemic lupus erythematosus. Arthritis Rheum 65(12):3165–3175. doi:10.​1002/​art.​38138 PubMedCrossRef
70.
Zurück zum Zitat Cappione A 3rd, Anolik JH, Pugh-Bernard A, Barnard J, Dutcher P, Silverman G, Sanz I (2005) Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus. J Clin Invest 115(11):3205–3216. doi:10.1172/JCI24179 PubMedCentralPubMedCrossRef Cappione A 3rd, Anolik JH, Pugh-Bernard A, Barnard J, Dutcher P, Silverman G, Sanz I (2005) Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus. J Clin Invest 115(11):3205–3216. doi:10.​1172/​JCI24179 PubMedCentralPubMedCrossRef
71.
Zurück zum Zitat Isenberg DA, Garton M, Reichlin MW, Reichlin M (1997) Long-term follow-up of autoantibody profiles in black female lupus patients and clinical comparison with Caucasian and Asian patients. Br J Rheumatol 36(2):229–233PubMedCrossRef Isenberg DA, Garton M, Reichlin MW, Reichlin M (1997) Long-term follow-up of autoantibody profiles in black female lupus patients and clinical comparison with Caucasian and Asian patients. Br J Rheumatol 36(2):229–233PubMedCrossRef
72.
Zurück zum Zitat van Vollenhoven RF, Bieber MM, Powell MJ, Gupta PK, Bhat NM, Richards KL, Albano SA, Teng NN (1999) VH4-34 encoded antibodies in systemic lupus erythematosus: a specific diagnostic marker that correlates with clinical disease characteristics. J Rheumatol 26(8):1727–1733PubMed van Vollenhoven RF, Bieber MM, Powell MJ, Gupta PK, Bhat NM, Richards KL, Albano SA, Teng NN (1999) VH4-34 encoded antibodies in systemic lupus erythematosus: a specific diagnostic marker that correlates with clinical disease characteristics. J Rheumatol 26(8):1727–1733PubMed
73.
Zurück zum Zitat Cappione A, Pugh-Bernard A, Sanz A (2002) Lupus VH4.34-encoded antibodies bind to a B220-specific glycoform of CD45 on the surface of human B lymphocytes. Arthritis Rheum 46:S222 Cappione A, Pugh-Bernard A, Sanz A (2002) Lupus VH4.34-encoded antibodies bind to a B220-specific glycoform of CD45 on the surface of human B lymphocytes. Arthritis Rheum 46:S222
74.
Zurück zum Zitat Pugh-Bernard AE, Silverman GJ, Cappione AJ, Villano ME, Ryan DH, Insel RA, Sanz I (2001) Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance. J Clin Invest 108(7):1061–1070. doi:10.1172/JCI12462 PubMedCentralPubMedCrossRef Pugh-Bernard AE, Silverman GJ, Cappione AJ, Villano ME, Ryan DH, Insel RA, Sanz I (2001) Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance. J Clin Invest 108(7):1061–1070. doi:10.​1172/​JCI12462 PubMedCentralPubMedCrossRef
78.
Zurück zum Zitat Jacobi AM, Reiter K, Mackay M, Aranow C, Hiepe F, Radbruch A, Hansen A, Burmester G, Diamond B, Lipsky PE, Dörner T (2008) Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: delineation by expression of CD27, IgD, and CD95. Arthritis Rheum 58(6):1762–1773PubMedCrossRef Jacobi AM, Reiter K, Mackay M, Aranow C, Hiepe F, Radbruch A, Hansen A, Burmester G, Diamond B, Lipsky PE, Dörner T (2008) Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: delineation by expression of CD27, IgD, and CD95. Arthritis Rheum 58(6):1762–1773PubMedCrossRef
80.
Zurück zum Zitat Cambier JC (2013) Autoimmunity risk alleles: hotspots in B cell regulatory signaling pathways. J Clin Invest:1–4. doi:10.1172/JCI69289 Cambier JC (2013) Autoimmunity risk alleles: hotspots in B cell regulatory signaling pathways. J Clin Invest:1–4. doi:10.​1172/​JCI69289
81.
Zurück zum Zitat Anolik JH, Barnard J, Cappione A, Pugh-Bernard AE, Felgar RE, Looney RJ, Sanz I (2004) Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum 50(11):3580–3590PubMedCrossRef Anolik JH, Barnard J, Cappione A, Pugh-Bernard AE, Felgar RE, Looney RJ, Sanz I (2004) Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum 50(11):3580–3590PubMedCrossRef
82.
Zurück zum Zitat Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, Sloand JA, Rosenblatt J, Sanz I (2004) B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50(8):2580–2589PubMedCrossRef Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, Sloand JA, Rosenblatt J, Sanz I (2004) B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50(8):2580–2589PubMedCrossRef
85.
Zurück zum Zitat Mei H, Schmidt S, Dorner T (2012) Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity. Arthritis Res Ther 14(Suppl 5):S1PubMedCentralPubMedCrossRef Mei H, Schmidt S, Dorner T (2012) Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity. Arthritis Res Ther 14(Suppl 5):S1PubMedCentralPubMedCrossRef
89.
Zurück zum Zitat Ginzler E, Wax S, Rajeswaran A, Copt S, Hillson J, Ramos E, Singer N (2012) Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther 14(1):R33PubMedCentralPubMedCrossRef Ginzler E, Wax S, Rajeswaran A, Copt S, Hillson J, Ramos E, Singer N (2012) Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther 14(1):R33PubMedCentralPubMedCrossRef
90.
Zurück zum Zitat Wallace DJ, Kalunian K, Petri MA, Strand V, Houssiau FA, Pike M, Kilgallen B, Bongardt S, Barry A, Kelley L, Gordon C (2013) Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis. doi:10.1136/annrheumdis-2012-202760 Wallace DJ, Kalunian K, Petri MA, Strand V, Houssiau FA, Pike M, Kilgallen B, Bongardt S, Barry A, Kelley L, Gordon C (2013) Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis. doi:10.​1136/​annrheumdis-2012-202760
91.
Zurück zum Zitat Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, Sloand J, Rosenblatt J, Sanz I (2004) B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50(8):2580–2589PubMedCrossRef Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, Sloand J, Rosenblatt J, Sanz I (2004) B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50(8):2580–2589PubMedCrossRef
92.
Zurück zum Zitat Vital EM, Dass S, Buch MH, Henshaw K, Pease CT, Martin MF, Ponchel F, Rawstron AC, Emery P (2011) B cell biomarkers of rituximab responses in systemic lupus erythematosus. Arthritis Rheum 63(10):3038–3047. doi:10.1002/art.30466 PubMedCrossRef Vital EM, Dass S, Buch MH, Henshaw K, Pease CT, Martin MF, Ponchel F, Rawstron AC, Emery P (2011) B cell biomarkers of rituximab responses in systemic lupus erythematosus. Arthritis Rheum 63(10):3038–3047. doi:10.​1002/​art.​30466 PubMedCrossRef
93.
Zurück zum Zitat Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CGM, St. Clair EW, Tchao NK, Viviano L, Ding L, Sejismundo LP, Mieras K, Ikle D, Jepson B, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Stone H, for the R-ITNRG (2013) Clinical outcomes of remission induction therapy for severe ANCA-associated vasculitis. Arthritis Rheum. doi:10.1002/art.38044 Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CGM, St. Clair EW, Tchao NK, Viviano L, Ding L, Sejismundo LP, Mieras K, Ikle D, Jepson B, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Stone H, for the R-ITNRG (2013) Clinical outcomes of remission induction therapy for severe ANCA-associated vasculitis. Arthritis Rheum. doi:10.​1002/​art.​38044
94.
Zurück zum Zitat Cambridge G, Leandro MJ, Teodorescu M, Manson J, Rahman A, Isenberg DA, Edwards JC (2006) B cell depletion therapy in systemic lupus erythematosus: effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum 54(11):3612–3622PubMedCrossRef Cambridge G, Leandro MJ, Teodorescu M, Manson J, Rahman A, Isenberg DA, Edwards JC (2006) B cell depletion therapy in systemic lupus erythematosus: effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum 54(11):3612–3622PubMedCrossRef
95.
Zurück zum Zitat Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH, Group HT (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis.[see comment]. N Engl J Med 358(7):676–688PubMedCrossRef Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH, Group HT (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis.[see comment]. N Engl J Med 358(7):676–688PubMedCrossRef
96.
Zurück zum Zitat Anolik J, Barnard J, Owen T, Zheng B, Kemshett S, Looney J, Sanz I (2007) Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis Rheum 56(9):3044–3056PubMedCrossRef Anolik J, Barnard J, Owen T, Zheng B, Kemshett S, Looney J, Sanz I (2007) Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis Rheum 56(9):3044–3056PubMedCrossRef
97.
Zurück zum Zitat Iwata S, Saito K, Tokunaga M, Yamaoka K, Nawata M, Yukawa S, Hanami K, Fukuyo S, Miyagawa I, Kubo S, Tanaka Y (2010) Phenotypic changes of lymphocytes in patients with systemic lupus erythematosus who are in longterm remission after B cell depletion therapy with rituximab. J Rheumatol. doi:10.3899/jrheum.100729 Iwata S, Saito K, Tokunaga M, Yamaoka K, Nawata M, Yukawa S, Hanami K, Fukuyo S, Miyagawa I, Kubo S, Tanaka Y (2010) Phenotypic changes of lymphocytes in patients with systemic lupus erythematosus who are in longterm remission after B cell depletion therapy with rituximab. J Rheumatol. doi:10.​3899/​jrheum.​100729
98.
Zurück zum Zitat Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki V, Iniotaki A, Moutsopoulos HM (2005) Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum 52(2):501–513PubMedCrossRef Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki V, Iniotaki A, Moutsopoulos HM (2005) Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum 52(2):501–513PubMedCrossRef
99.
Zurück zum Zitat van de Veerdonk FL, Lauwerys B, Marijnissen RJ, Timmermans K, Di Padova F, Koenders MI, Gutierrez-Roelens I, Durez P, Netea MG, van der Meer JWM, van den Berg WB, Joosten LAB (2011) The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum 63(6):1507–1516. doi:10.1002/art.30314 PubMedCrossRef van de Veerdonk FL, Lauwerys B, Marijnissen RJ, Timmermans K, Di Padova F, Koenders MI, Gutierrez-Roelens I, Durez P, Netea MG, van der Meer JWM, van den Berg WB, Joosten LAB (2011) The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum 63(6):1507–1516. doi:10.​1002/​art.​30314 PubMedCrossRef
100.
Zurück zum Zitat Stasi R, Cooper N, Del Poeta G, Stipa E, Evangelista ML, Abruzzese E, Amadori S (2008) Analysis of regulatory T cell changes in patients with idiopathic thrombocytopenic purpura receiving B-cell depleting therapy with rituximab. Blood:blood-2007-2012-129262. doi:10.1182/blood-2007-12-129262 Stasi R, Cooper N, Del Poeta G, Stipa E, Evangelista ML, Abruzzese E, Amadori S (2008) Analysis of regulatory T cell changes in patients with idiopathic thrombocytopenic purpura receiving B-cell depleting therapy with rituximab. Blood:blood-2007-2012-129262. doi:10.​1182/​blood-2007-12-129262
101.
Zurück zum Zitat Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, Aranow C, Wellborne FR, Abud-Mendoza C, Hough DR, Pineda L, Migone T-S, Zhong ZJ, Freimuth WW, Chatham WW, on behalf of the B, Groups B-S (2012) Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum 64(7):2328–2337. doi:10.1002/art.34400 PubMedCentralPubMedCrossRef Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, Aranow C, Wellborne FR, Abud-Mendoza C, Hough DR, Pineda L, Migone T-S, Zhong ZJ, Freimuth WW, Chatham WW, on behalf of the B, Groups B-S (2012) Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum 64(7):2328–2337. doi:10.​1002/​art.​34400 PubMedCentralPubMedCrossRef
102.
Zurück zum Zitat Jacobi AM, Huang W, Wang T, Freimuth W, Sanz I, Furie R, Mackay M, Aranow C, Diamond B, Davidson A (2010) Effect of long-term belimumab treatment on b cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum 62(1):201–210PubMedCentralPubMedCrossRef Jacobi AM, Huang W, Wang T, Freimuth W, Sanz I, Furie R, Mackay M, Aranow C, Diamond B, Davidson A (2010) Effect of long-term belimumab treatment on b cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum 62(1):201–210PubMedCentralPubMedCrossRef
103.
Zurück zum Zitat Wallace DJ, Gordon C, Strand V, Hobbs K, Petri M, Kalunian K, Houssiau F, Tak PP, Isenberg DA, Kelley L, Kilgallen B, Barry AN, Wegener WA, Goldenberg DM (2013) Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up. Rheumatology (Oxford). doi:10.1093/rheumatology/ket129 Wallace DJ, Gordon C, Strand V, Hobbs K, Petri M, Kalunian K, Houssiau F, Tak PP, Isenberg DA, Kelley L, Kilgallen B, Barry AN, Wegener WA, Goldenberg DM (2013) Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up. Rheumatology (Oxford). doi:10.​1093/​rheumatology/​ket129
104.
Zurück zum Zitat Jacobi AM, Goldenberg DM, Hiepe F, Radbruch A, Burmester GR, Dörner T (2008) Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls. Ann Rheum Dis 67(4):450–457. doi:10.1136/ard.2007.075762 PubMedCrossRef Jacobi AM, Goldenberg DM, Hiepe F, Radbruch A, Burmester GR, Dörner T (2008) Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls. Ann Rheum Dis 67(4):450–457. doi:10.​1136/​ard.​2007.​075762 PubMedCrossRef
105.
Zurück zum Zitat Daridon C, Blassfeld D, Reiter K, Mei H, Giesecke C, Goldenberg D, Hansen A, Hostmann A, Frolich D, Dorner T (2010) Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus. Arthritis Res Ther 12(6):R204PubMedCentralPubMedCrossRef Daridon C, Blassfeld D, Reiter K, Mei H, Giesecke C, Goldenberg D, Hansen A, Hostmann A, Frolich D, Dorner T (2010) Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus. Arthritis Res Ther 12(6):R204PubMedCentralPubMedCrossRef
Metadaten
Titel
Rationale for B cell targeting in SLE
verfasst von
Iñaki Sanz
Publikationsdatum
01.05.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Seminars in Immunopathology / Ausgabe 3/2014
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-014-0430-z

Weitere Artikel der Ausgabe 3/2014

Seminars in Immunopathology 3/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.