rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2014-545-552rsp-1990Research ArticleПРОГРЕСС В РЕВМАТОЛОГИИ В XXI ВЕКЕPROGRESS IN RHEUMATOLOGY IN THE XXI CENTURYКлиническое значение BAFF/BLyS и APRIL при системной красной волчанке и ревматоидном артритеCLINICAL SIGNIFICANCE OF BAFF/BLyS AND APRIL IN SYSTEMIC LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITISСупоницкаяЕ. В.SuponitskyaE. V.

младший научный сотрудник лаборатории клинической иммунологии и молекулярной биологии ревматических заболеваний

ekaterina.s@mtu-net.ruАлександроваЕ. Н.AleksandrovaE. N.

заведующая клинической лабораторией иммунологии и молекулярной биологии ревматических заболеваний

НасоновЕ. Л.NasonovE. L.

директор

ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, РоссияРоссияV.A. Nasonova Research Institute of Rheumatology, Moscow, RussiaRussian Federation201407102014525545552Copyright © Супоницкая Е.В., Александрова Е.Н., Насонов Е.Л., 20142014Супоницкая Е.В., Александрова Е.Н., Насонов Е.Л.Suponitskya E.V., Aleksandrova E.N., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/1990

Рассматриваются механизмы действия цитокинов BAFF/BLyS и APRIL при иммуновоспалительных ревматических заболеваниях, зависимость клинико-лабораторной активности ревматоидного артрита (РА) и системной красной волчанки (СКВ) от уровней этих цитокинов, влияние терапии генно-инженерными биологическими препаратами на уровень BAFF/BLyS и APRIL при РА и СКВ.

The present work is devoted to mechanisms of action of cytokines BAFF/BLyS and APRIL in immune inflammatory rheumatic diseases; correlation between the level of this cytokines and activity of rheumatic arthritis and systemic lupus erythematosus (SLE); impact of the biologic agents on the level of BAFF/BLyS and APRIL at RA and SLE.

BAFF/BLySAPRILревматоидный артритсистемная красная волчанкагенно-инженер- ные биологические препаратыBAFF/BLySAPRILrheumatoid arthritissystemic lupus erythematosusgenetically engineered biologic drugsReferencesDö rner T. Crossroads of B cell activation in autoimmunity: rationale of targeting B cells. J Rheumatol 2006;33(Suppl 77):3–11.Dö rner T. Crossroads of B cell activation in autoimmunity: rationale of targeting B cells. J Rheumatol 2006;33(Suppl 77):3–11.Dö rner T, Jacobi AM, Lipsky PE. B cells in autoimmunity. Arthritis Res Ther. 2009;11(5):247. DOI: 10.1186/ar2780. Epub 2009 Oct 14.Dö rner T, Jacobi AM, Lipsky PE. B cells in autoimmunity. Arthritis Res Ther. 2009;11(5):247. DOI: 10.1186/ar2780. Epub 2009 Oct 14.Mackay F, Schneider P, Rennert P, Browning J. BAFF and APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003;21:231–64. DOI: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141152.Mackay F, Schneider P, Rennert P, Browning J. BAFF and APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003;21:231–64. DOI: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141152.Ng LG, Mackay CR, Mackay F. The BAFF/APRIL system: life beyond B lymphocytes. Mol Immunol. 2005;42(7):763–72. DOI: http://dx.doi.org/10.1016/j.molimm.2004.06.041. Epub 2004 Dec 8.Ng LG, Mackay CR, Mackay F. The BAFF/APRIL system: life beyond B lymphocytes. Mol Immunol. 2005;42(7):763–72. DOI: http://dx.doi.org/10.1016/j.molimm.2004.06.041. Epub 2004 Dec 8.Batten M, Fletcher C, Ng LG, et al. TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma. J Immunol. 2004;172(2):812–22. DOI: http://dx.doi.org/10.4049/jimmunol. 172.2.812.Batten M, Fletcher C, Ng LG, et al. TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma. J Immunol. 2004;172(2):812–22. DOI: http://dx.doi.org/10.4049/jimmunol. 172.2.812.Vallerskog T, Heimburger M, Gunnarsson I, et al. Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther. 2006;8(6):R167. DOI: http://dx.doi.org/10.1186/ar2076.Vallerskog T, Heimburger M, Gunnarsson I, et al. Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther. 2006;8(6):R167. DOI: http://dx.doi.org/10.1186/ar2076.Moore PA, Belvedere O, Orr A, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285(5425):260–3. DOI: http://dx.doi.org/10.1126/science. 285.5425.260.Moore PA, Belvedere O, Orr A, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285(5425):260–3. DOI: http://dx.doi.org/10.1126/science. 285.5425.260.Ohata J, Zvaifler NJ, Nishio M, et al. Fibroblast-like synoviocytes of mesenchymal origin express functional B cell-activating factor of the TNF family in response to proinflammatory cytokines. J Immunol. 2005;174(2):864–70. DOI: http://dx.doi.org/10.4049/jimmunol.174.2.864.Ohata J, Zvaifler NJ, Nishio M, et al. Fibroblast-like synoviocytes of mesenchymal origin express functional B cell-activating factor of the TNF family in response to proinflammatory cytokines. J Immunol. 2005;174(2):864–70. DOI: http://dx.doi.org/10.4049/jimmunol.174.2.864.Khare SD, Sarosi I, Xia XZ, et al. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci USA. 2000;97(7):3370–5. DOI: http://dx.doi.org/10.1073/pnas.97.7.3370.Khare SD, Sarosi I, Xia XZ, et al. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci USA. 2000;97(7):3370–5. DOI: http://dx.doi.org/10.1073/pnas.97.7.3370.Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190(11):1697–710. DOI: http://dx.doi.org/10.1084/jem.190.11.1697.Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190(11):1697–710. DOI: http://dx.doi.org/10.1084/jem.190.11.1697.Gross JA, Johnston J, Mudri S, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000;404(6781):995–9. DOI: http://dx.doi.org/10.1038/35010115.Gross JA, Johnston J, Mudri S, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000;404(6781):995–9. DOI: http://dx.doi.org/10.1038/35010115.Dillon SR, Gross JA, Ansell SM, Novak AJ. An APRIL to remember: novel TNF ligands as therapeutic targets. Nat Rev Drug Discov. 2006;5(3):235–46. DOI: http://dx.doi.org/10.1038/nrd1982.Dillon SR, Gross JA, Ansell SM, Novak AJ. An APRIL to remember: novel TNF ligands as therapeutic targets. Nat Rev Drug Discov. 2006;5(3):235–46. DOI: http://dx.doi.org/10.1038/nrd1982.Jacobi AM, Dorner T. Current aspects of anti-CD20 therapy in rheumatoid arthritis. Curr Opin Pharmacol. 2010;10(3):316–21. DOI: 10.1016/j.coph.2010.02.002. Epub 2010 Feb 26.Jacobi AM, Dorner T. Current aspects of anti-CD20 therapy in rheumatoid arthritis. Curr Opin Pharmacol. 2010;10(3):316–21. DOI: 10.1016/j.coph.2010.02.002. Epub 2010 Feb 26.Tan S-M, Xu D, Roschke V, et al. Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis. Arthritis Rheum. 2003;48(4):982–92. DOI: http://dx.doi.org/10.1002/art.10860.Tan S-M, Xu D, Roschke V, et al. Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis. Arthritis Rheum. 2003;48(4):982–92. DOI: http://dx.doi.org/10.1002/art.10860.Wang B, Feliciani C, Freed I, et al. Insights into molecular mechanisms of contact hypersensitivity gained from gene knockout studies. J Leukoc Biol. 2001;70(2):185–91.Wang B, Feliciani C, Freed I, et al. Insights into molecular mechanisms of contact hypersensitivity gained from gene knockout studies. J Leukoc Biol. 2001;70(2):185–91.Fernandez L, Salinas GF, Rocha C, et al. The TNF family member APRIL dampens collagen-induced arthritis. Ann Rheum Dis. 2013;72(8):1367–74. DOI: 10.1136/annrheumdis-2012-202382. Epub 2012 Nov 24.Fernandez L, Salinas GF, Rocha C, et al. The TNF family member APRIL dampens collagen-induced arthritis. Ann Rheum Dis. 2013;72(8):1367–74. DOI: 10.1136/annrheumdis-2012-202382. Epub 2012 Nov 24.Jacob CO, Guo S, Jacob N, et al. Dispensability of APRIL to the development of systemic lupus erythematosus in NZM 2328 mice. Arthritis Rheum. 2012;64(5):1610–9. DOI: 10.1002/art.33458.Jacob CO, Guo S, Jacob N, et al. Dispensability of APRIL to the development of systemic lupus erythematosus in NZM 2328 mice. Arthritis Rheum. 2012;64(5):1610–9. DOI: 10.1002/art.33458.Groom J, Kalled SL, Cutler AH, et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjö gren's syndrome. J Clin Invest. 2002;109(1):59–68. DOI: http://dx.doi.org/10.1172/JCI0214121.Groom J, Kalled SL, Cutler AH, et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjö gren's syndrome. J Clin Invest. 2002;109(1):59–68. DOI: http://dx.doi.org/10.1172/JCI0214121.Zhang J, Roschke V, Baker KP, et al. A role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol. 2001;166(1):6–10. DOI: http://dx.doi.org/10.4049/jimmunol. 166.1.6.Zhang J, Roschke V, Baker KP, et al. A role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol. 2001;166(1):6–10. DOI: http://dx.doi.org/10.4049/jimmunol. 166.1.6.Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immunebased rheumatic diseases. Arthritis Rheum. 2001;44(6):1313–9. DOI: http://dx.doi.org/10.1002/1529-0131(200106)44:6%3C1313::AID-ART223%3E3.0.CO;2-S.Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immunebased rheumatic diseases. Arthritis Rheum. 2001;44(6):1313–9. DOI: http://dx.doi.org/10.1002/1529-0131(200106)44:6%3C1313::AID-ART223%3E3.0.CO;2-S.Stohl W, Metyas S, Tan SM, et al. B lymphocyte stimulator overexpressionStohl W, Metyas S, Tan SM, et al. B lymphocyte stimulator overexpressionin patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum. 2003;48(12):3475–86. DOI: http://dx.doi.org/10.1002/art.11354.in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum. 2003;48(12):3475–86. DOI: http://dx.doi.org/10.1002/art.11354.Mariette X, Roux S, Zhang J, et al. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjö gren's syndrome. Ann Rheum Dis. 2003;62(2):168–71. DOI: http://dx.doi.org/10.1136/ard.62.2.168.Mariette X, Roux S, Zhang J, et al. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjö gren's syndrome. Ann Rheum Dis. 2003;62(2):168–71. DOI: http://dx.doi.org/10.1136/ard.62.2.168.Bosello S, Youinou P, Daridon C, et al. Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis. J Rheumatol. 2008;35(7):1256–64.Bosello S, Youinou P, Daridon C, et al. Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis. J Rheumatol. 2008;35(7):1256–64.Moura RA, Cascao R, Perpetuo I, et al. Cytokine pattern in very early rheumatoid arthritis favours B-cell activation and survival. Rheumatology (Oxford). 2011;50(2):278–82. DOI: 10.1093/rheumatology/keq338. Epub 2010 Nov 2.Moura RA, Cascao R, Perpetuo I, et al. Cytokine pattern in very early rheumatoid arthritis favours B-cell activation and survival. Rheumatology (Oxford). 2011;50(2):278–82. DOI: 10.1093/rheumatology/keq338. Epub 2010 Nov 2.Gottenberg JE, Miceli-Richard C, Ducot B, et al. Markers of Blymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort. Arthritis Res Ther. 2009;11(4):R114. DOI: 10.1186/ar2773. Epub 2009 Jul 23.Gottenberg JE, Miceli-Richard C, Ducot B, et al. Markers of Blymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort. Arthritis Res Ther. 2009;11(4):R114. DOI: 10.1186/ar2773. Epub 2009 Jul 23.Becker-Merok A, Nikolaisen C, Nossent HC. B-lymphocyte activating factor in systemic lupus erythematosus and rheumatoid arthritis in relation to autoantibody levels, disease measures and time. Lupus. 2006;15(9):570. DOI: http://dx.doi.org/10.1177/0961203306071871.Becker-Merok A, Nikolaisen C, Nossent HC. B-lymphocyte activating factor in systemic lupus erythematosus and rheumatoid arthritis in relation to autoantibody levels, disease measures and time. Lupus. 2006;15(9):570. DOI: http://dx.doi.org/10.1177/0961203306071871.Stohl W. B lymphocyte stimulator protein levels in systemic lupus erythematosus and other diseases. Curr Rheumatol Rep. 002;4(4):345–50. DOI: http://dx.doi.org/10.1007/s11926-002-0044-7.Stohl W. B lymphocyte stimulator protein levels in systemic lupus erythematosus and other diseases. Curr Rheumatol Rep. 002;4(4):345–50. DOI: http://dx.doi.org/10.1007/s11926-002-0044-7.Pers JO, Daridon C, Devauchelle V, et al. BAFF overexpression is associated with autoantibody production in autoimmune diseases. Ann N Y Acad Sci. 2005;1050:34–9. DOI: http://dx.doi.org/10.1196/annals.1313.004.Pers JO, Daridon C, Devauchelle V, et al. BAFF overexpression is associated with autoantibody production in autoimmune diseases. Ann N Y Acad Sci. 2005;1050:34–9. DOI: http://dx.doi.org/10.1196/annals.1313.004.Candon S, Gottenberg JE, Bengoufa D, et al. Quantitative assessment of antibodies to ribonucleoproteins in primary Sjö gren syndrome: correlation with B-cell biomarkers and disease activity. Ann Rheum Dis. 2009;68(7):1208–12. DOI: http://dx.doi.org/10.1136/ard.2008.095257.Candon S, Gottenberg JE, Bengoufa D, et al. Quantitative assessment of antibodies to ribonucleoproteins in primary Sjö gren syndrome: correlation with B-cell biomarkers and disease activity. Ann Rheum Dis. 2009;68(7):1208–12. DOI: http://dx.doi.org/10.1136/ard.2008.095257.Schneeweis C, Rafalowicz M, Feist E, et al. Increased levels of BLyS and sVCAM-1 in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV). Clin Exp Rheumatol. 2010;28(1 Suppl 57):62–6.Schneeweis C, Rafalowicz M, Feist E, et al. Increased levels of BLyS and sVCAM-1 in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV). Clin Exp Rheumatol. 2010;28(1 Suppl 57):62–6.Petri M, Stohl W, Chatham W, et al. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008;58(8):2453–9. DOI: 10.1002/art.23678.Petri M, Stohl W, Chatham W, et al. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008;58(8):2453–9. DOI: 10.1002/art.23678.Collins CE, Gavin AL, Migone TS, et al. 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(1):R6. DOI: http://dx.doi.org/10.1186/ar1855.Collins CE, Gavin AL, Migone TS, et al. 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(1):R6. DOI: http://dx.doi.org/10.1186/ar1855.La DT, Collins CE, Yang HT, et al. B lymphocyte stimulator expression in patients with rheumatoid arthritis treated with tumour necrosis factor a antagonists: differential effects between good and poor clinical responders. Ann Rheum Dis. 2008 Aug;67(8):1132–8. DOI: http://dx.doi.org/10.1136/ard.2007.079954.La DT, Collins CE, Yang HT, et al. B lymphocyte stimulator expression in patients with rheumatoid arthritis treated with tumour necrosis factor a antagonists: differential effects between good and poor clinical responders. Ann Rheum Dis. 2008 Aug;67(8):1132–8. DOI: http://dx.doi.org/10.1136/ard.2007.079954.Chu VT, Enghard P, Schurer S, 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(7):2083–93. DOI: 10.1002/art.24628.Chu VT, Enghard P, Schurer S, 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(7):2083–93. DOI: 10.1002/art.24628.Cambridge G, Isenberg DA, Edwards JCW, et al. B cell depletion therapy in systemic lupus erythaematosus: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response. Ann Rheum Dis. 2008;67(7):1011–6. Epub 2007 Oct 25.Cambridge G, Isenberg DA, Edwards JCW, et al. B cell depletion therapy in systemic lupus erythaematosus: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response. Ann Rheum Dis. 2008;67(7):1011–6. Epub 2007 Oct 25.Mariette X, Kivitz A, Isaacs JD, et al. Effectiveness of rituximab (RTX) + methotrexate (MTX) in patients (pts) with early active rheumatoid arthritis (RA) and disease charaxteristics associated with poor outcomes. Arthritis Rheum. 2009;60 Suppl:S631 [1687].Mariette X, Kivitz A, Isaacs JD, et al. Effectiveness of rituximab (RTX) + methotrexate (MTX) in patients (pts) with early active rheumatoid arthritis (RA) and disease charaxteristics associated with poor outcomes. Arthritis Rheum. 2009;60 Suppl:S631 [1687].Vital E, Cuthbert R, Horner E, et al. High serum B-cell activating factor (BAFF) predicts good clinical response to rituximab in RA: pilot data. Ann Rheum Dis. 2010;69:A11–2. DOI: http://dx.doi.org/10.1136/ard.2010.129585b.Vital E, Cuthbert R, Horner E, et al. High serum B-cell activating factor (BAFF) predicts good clinical response to rituximab in RA: pilot data. Ann Rheum Dis. 2010;69:A11–2. DOI: http://dx.doi.org/10.1136/ard.2010.129585b.Vital EM, Cuthbert RJ, Dass SP, et al. Serum cytokine profil predicts response to rituximab therapy in rheumatoid arthritis. Arthritis Rheum. 2010;62 Suppl 10:1126.Vital EM, Cuthbert RJ, Dass SP, et al. Serum cytokine profil predicts response to rituximab therapy in rheumatoid arthritis. Arthritis Rheum. 2010;62 Suppl 10:1126.Cornec D, Avouac J, Youinou P, Saraux A. Critical analysis of rituximab-induced serological changes in connective tissue diseases. Autoimmun Rev. 2009;8(6):515–9. DOI: 10.1016/j.autrev.2009.01.007. Epub 2009 Jan 30.Cornec D, Avouac J, Youinou P, Saraux A. Critical analysis of rituximab-induced serological changes in connective tissue diseases. Autoimmun Rev. 2009;8(6):515–9. DOI: 10.1016/j.autrev.2009.01.007. Epub 2009 Jan 30.Lavie F, Miceli-Richard C, Ittah M, et al. Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production. Ann Rheum Dis. 2007;66(5):700–3. DOI: http://dx.doi.org/10.1136/ard.2006.060772. Epub 2006 Oct 13.Lavie F, Miceli-Richard C, Ittah M, et al. Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production. Ann Rheum Dis. 2007;66(5):700–3. DOI: http://dx.doi.org/10.1136/ard.2006.060772. Epub 2006 Oct 13.Cambridge G, Stohl W, Leandro MJ, et al. Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum. 2006;54(3):723–32. DOI: http://dx.doi.org/10.1002/art.21650.Cambridge G, Stohl W, Leandro MJ, et al. Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum. 2006;54(3):723–32. DOI: http://dx.doi.org/10.1002/art.21650.Ferraccioli G, Tolusso B, Pallavicini FB, et al. Biomarkers predictors of good EULAR response to B cell depletion therapy (BCDT) in seropositive rheumatoid arthritis patients. Arthritis Rheum. 2010;62 Suppl 10:1098.Ferraccioli G, Tolusso B, Pallavicini FB, et al. Biomarkers predictors of good EULAR response to B cell depletion therapy (BCDT) in seropositive rheumatoid arthritis patients. Arthritis Rheum. 2010;62 Suppl 10:1098.De la Torre I, Moura L, Leandro R, et al. BAFF binding receptors (BBR) related to relapse after rituximab in patients with rheumatoid arthritis (RA). Arthritis Rheum. 2010;62 Suppl 10:739.De la Torre I, Moura L, Leandro R, et al. BAFF binding receptors (BBR) related to relapse after rituximab in patients with rheumatoid arthritis (RA). Arthritis Rheum. 2010;62 Suppl 10:739.Moura RA, de la Torre I, Leandro R, et al. BAFF-R expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis (RA) following B cell depletion therapy. Ann Rheum Dis. 2010;69 Suppl 3:379 [FRI0194].Moura RA, de la Torre I, Leandro R, et al. BAFF-R expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis (RA) following B cell depletion therapy. Ann Rheum Dis. 2010;69 Suppl 3:379 [FRI0194].Stohl W, Metyas S, Tan S-M, et al. Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis. 2004;63(9):1096–103. DOI: http://dx.doi.org/10.1136/ard.2003.018663.Stohl W, Metyas S, Tan S-M, et al. Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis. 2004;63(9):1096–103. DOI: http://dx.doi.org/10.1136/ard.2003.018663.Koyama T, Tsukamoto H, Miyagi Y, et al. Raised serum APRIL levels in patients with systemic lupus erythematosus. Ann Rheum Dis. 2005;64(7):1065–7. DOI: http://dx.doi.org/10.1136/ard.2004.022491. Epub 2004 Dec 2.Koyama T, Tsukamoto H, Miyagi Y, et al. Raised serum APRIL levels in patients with systemic lupus erythematosus. Ann Rheum Dis. 2005;64(7):1065–7. DOI: http://dx.doi.org/10.1136/ard.2004.022491. Epub 2004 Dec 2.Seyler TM, Park YW, Takemura S, et al. BLyS and APRIL in rheumatoid arthritis. J Clin Invest. 2005;115(11):3083–92. DOI: http://dx.doi.org/10.1172/JCI25265. Epub 2005 Oct 20.Seyler TM, Park YW, Takemura S, et al. BLyS and APRIL in rheumatoid arthritis. J Clin Invest. 2005;115(11):3083–92. DOI: http://dx.doi.org/10.1172/JCI25265. Epub 2005 Oct 20.Treamtrakanpon W, Tantivitayakul P, Benjachat T, et al. APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis. Arthritis Res Ther. 2012;14(6):R252. DOI: 10.1186/ar4095.Treamtrakanpon W, Tantivitayakul P, Benjachat T, et al. APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis. Arthritis Res Ther. 2012;14(6):R252. DOI: 10.1186/ar4095.Morel J, Hahne M. To target or not to target APRIL in systemic lupus erythematosus: that is the question! Arthritis Res Ther. 2013;15(1):107. DOI: 10.1186/ar4160.Morel J, Hahne M. To target or not to target APRIL in systemic lupus erythematosus: that is the question! Arthritis Res Ther. 2013;15(1):107. DOI: 10.1186/ar4160.Morel J, Roubille C, Planelles L, et al. Serum levels of tumour necrosis factor family members a proliferation-inducing ligand (APRIL) and B lymphocyte stimulator (BLyS) are inversely correlated in systemic lupus erythematosus. Ann Rheum Dis. 2009;68(6):997–1002. DOI: 10.1136/ard.2008.090928. Epub 2008 Aug 2.Morel J, Roubille C, Planelles L, et al. Serum levels of tumour necrosis factor family members a proliferation-inducing ligand (APRIL) and B lymphocyte stimulator (BLyS) are inversely correlated in systemic lupus erythematosus. Ann Rheum Dis. 2009;68(6):997–1002. DOI: 10.1136/ard.2008.090928. Epub 2008 Aug 2.Browning JL. B cells move to centre stage: novel opportunities for autoimmune disease treatment. Nat Rev Drug Discov. 2006;5(7):564–76. DOI: http://dx.doi.org/10.1038/nrd2085.Browning JL. B cells move to centre stage: novel opportunities for autoimmune disease treatment. Nat Rev Drug Discov. 2006;5(7):564–76. DOI: http://dx.doi.org/10.1038/nrd2085.Dö rner T, Radbruch A, Burmester GR. B-cell-directed therapies for autoimmune disease. Nat Rev Rheumatol. 2009;5(8):433–41. DOI: 10.1038/nrrheum.2009.141. Epub 2009 Jul 7. Review.Dö rner T, Radbruch A, Burmester GR. B-cell-directed therapies for autoimmune disease. Nat Rev Rheumatol. 2009;5(8):433–41. DOI: 10.1038/nrrheum.2009.141. Epub 2009 Jul 7. Review.Silverman GJ. Therapeutic B cell depletion and regeneration in rheumatoid arthritis. Emerging patterns and paradigms. Arthritis Rheum. 2006;54(8):2356–67. DOI: http://dx.doi.org/10.1002/art.22020.Silverman GJ. Therapeutic B cell depletion and regeneration in rheumatoid arthritis. Emerging patterns and paradigms. Arthritis Rheum. 2006;54(8):2356–67. DOI: http://dx.doi.org/10.1002/art.22020.Manzi S, Sanchez-Guerrero J, Merrill JT, et al. BLISS-52 and BLISS-76 Study Groups: 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(11):1833–8. DOI: 10.1136/annrheumdis-2011-200831. Epub 2012 May 1.Manzi S, Sanchez-Guerrero J, Merrill JT, et al. BLISS-52 and BLISS-76 Study Groups: 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(11):1833–8. DOI: 10.1136/annrheumdis-2011-200831. Epub 2012 May 1.Navarra SV, Guzman RM, Gallacher AE, et al. BLISS-52 Study Group: Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-31. DOI: 10.1016/S0140-6736(10)61354-2. Epub 2011 Feb 4.Navarra SV, Guzman RM, Gallacher AE, et al. BLISS-52 Study Group: Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-31. DOI: 10.1016/S0140-6736(10)61354-2. Epub 2011 Feb 4.Stohl W, Hiepe F, Latinis KM, et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in the patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64(7):2328–37. DOI: 10.1002/art.34400.Stohl W, Hiepe F, Latinis KM, et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in the patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64(7):2328–37. DOI: 10.1002/art.34400.Van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012;71(8):1343–9. DOI: 10.1136/annrheumdis-2011-200937. Epub 2012 Feb 15.Van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012;71(8):1343–9. DOI: 10.1136/annrheumdis-2011-200937. Epub 2012 Feb 15.McKay J, Chwalinska-Sadowska H, Boling E, et al. LBRA01 Study Group: Belimumab, a fully human monoclonal antibody to B-lymphocyte stimulator, combined with standard care of therapy reduces the signs and symptoms of rheumatoid arthritis in a heterogeneous subject population. Arthritis Rheum. 2005;(52):S710–1.McKay J, Chwalinska-Sadowska H, Boling E, et al. LBRA01 Study Group: Belimumab, a fully human monoclonal antibody to B-lymphocyte stimulator, combined with standard care of therapy reduces the signs and symptoms of rheumatoid arthritis in a heterogeneous subject population. Arthritis Rheum. 2005;(52):S710–1.Ginzler EM, Wax S, Rajeswaran A, et al. Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther. 2012;14(1):R33. DOI: 10.1186/ar3738.Ginzler EM, Wax S, Rajeswaran A, et al. Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther. 2012;14(1):R33. DOI: 10.1186/ar3738.Genovese MC, Kinnman N, de la Bourdonnaye G, et al. Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor antagonist therapy: results of a phase II, randomized, placebo-controlled, dose-finding trial. Arthritis Rheum. 2011;63(7):1793–803. DOI: 10.1002/art.30373.Genovese MC, Kinnman N, de la Bourdonnaye G, et al. Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor antagonist therapy: results of a phase II, randomized, placebo-controlled, dose-finding trial. Arthritis Rheum. 2011;63(7):1793–803. DOI: 10.1002/art.30373.

The authors declare that there are no conflicts of interest present.