B细胞与狼疮肾炎治疗进展
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摘要
狼疮肾炎(LN)是系统性红斑狼疮(SLE)发生率较高的并发症,其发病机制目前尚未完全阐明,现主要通过糖皮质激素及经典免疫抑制剂治疗,但由于这些药物使用后会引起一系列不良反应,使得LN治疗变得更为棘手。B细胞在SLE/LN中的作用已得到广泛认可,目前已研制出针对B细胞不同靶点的生物制剂,这为治疗LN提供了新的方向。本文就B细胞在LN中的作用及相关生物制剂在LN治疗中的进展做一综述。
Lupus nephritis(LN) is a complication of systemic lupus erythematosus(SLE) with high incidence. Its pathogenesis has not yet been fully elucidated. It is mainly treated with glucocorticoids and classic immunosuppressive agents. The use of these drugs can cause a series of related complications, which makes the LN treatment become more difficult. The role of B cells in SLE/LN has been widely recognized, and biological agents targeting different targets of B cells have been developed to provide a new direction for the treatment of LN. This article reviews the role of B cells in LN and the progress of related biological agents in the treatment of LN.
Lupus nephritis(LN) is a complication of systemic lupus erythematosus(SLE) with high incidence. Its pathogenesis has not yet been fully elucidated. It is mainly treated with glucocorticoids and classic immunosuppressive agents. The use of these drugs can cause a series of related complications, which makes the LN treatment become more difficult. The role of B cells in SLE/LN has been widely recognized, and biological agents targeting different targets of B cells have been developed to provide a new direction for the treatment of LN. This article reviews the role of B cells in LN and the progress of related biological agents in the treatment of LN.
引文
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[14] Schwarting A, Relle M, Meineck M, et al. Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse and men[J]. Lupus,2018,27(2):243-256.
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[17] Weinstein JS,Delano MJ,Xu Y,et al. Maintenance of anti-Sm/RNP autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory B cells[J]. J Immunol,2013,190(8): 3916-3927.
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[22] Dall'Era M,Chakravarty E,Wallace D,et al. Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating trial[J].Arthritis Rheum,2007,56(12):4142-4150.
[23] Figgett WA,Deliyanti D,Fairfax KA,et al.Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers[J].J Autoimmun,2015,61:9-16.
[24] Dall'Era M,Davis J.CTLA4Ig: a novel inhibitor of costimulation[J]. Lupu,2004,13(5):372-376.
[25] Wofsy D,Hillson JL,Diamond B.Abatacept for lupus nephritis: alternative definitions of complete responsesupport conflicting conclusions[J]. Arthritis Rheum,2012,64(11):3660-3665.
[26] Furie R,Nicholls K,Cheng TT,et al.Efficacy and safety of abatacept in lupus nephritis a twelve month,randomized,double-blind study[J].Arthritis Rheumatol,2014,66(2):379-389.
[27] Elgueta R,Benson MJ,de Vries VC,et al. Molecular mechanism and function of CD40/CD40L engagement in the immune system[J]. Immunol Rev,2009,229(1):152-172.
[28] Sfikakis PP,Boletis JN,Lionaki S,et al. 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[J]. Arthritis Rheum,2005,52(2): 501-513.
[29] Boumpas DT,Furie R,Manzi S,et al. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreaseshematuria in patients with proliferative lupus glomerulonephritis[J].Arthritis Rheum,2003,48(3): 719-727.
[30] Shock A,Burkly L,Wakefield I,et al.CDP7657,an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study[J]. Arthritis Res Ther,2015,17: 234.
[31] Albach FN,Wagner F, Hüser A,et al.Safety,pharmacokinetics and pharmacodynamics of single rising doses of BI 655064,an antagonistic anti-CD40 antibody in healthy subjects: a potential novel treatment for autoimmune diseases[J]. Eur J Clin Pharmacol,2018,74(2):161-169.
[2] Browning JL. B cells move to centre stage: novel opportunities for autoimmune disease treatment[J]. Nat Rev Drug Discov,2006,5(7):564-576.
[3] Plosker GL, Figgitt DP. Rituximab: a review of its use in non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia[J]. Drugs,2003,63(8): 803-843.
[4] Rovin BH,Furie R,Latinis K,et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study[J]. Arthritis Rheum,2012,64(4):1215-1226.
[5] Contis A,Vanquaethem H,Truchetet ME, et al. Analysis of the effectiveness and safety of rituximab in patients with refractory lupus nephritis: a chart review[J].Clin Rheumatol,2016,35(2):517-522
[6] Manou-Stathopoulou S,Robson MG. Risk of clinical deterioration in patients with lupus nephritis receiving rituximab[J].Lupus,2016,25(12):1299-1306
[7] Reddy V,Klein C,Isenberg DA,et al.Obinutuzumab induces superior B-cell cytotoxicity to rituximab in rheumatoid arthritis and systemic lupus[J]. Rheumatology (Oxford),2017,56(7):1227-1237.
[8] M?ssner E,Brünker P, Moser S,et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity[J]. Blood, 2010,115(22): 4393-4402.
[9] O’Keefe TL, Williams GT, Batista FD, et al. Deficiency in CD22, a B cell-specific inhibitory receptor,is sufficient to predispose to development of high affinity autoantibodies[J]. J Exp Med,1999,189(8):1307-1313.
[10] Dorner T,Kaufmann J,Wegener WA,et al. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus[J]. Arthritis Res Ther,2006,8(3): R74.
[11] Clowse ME,Wallace DJ,Furie RA,et al. Efficacy and safety of epratuzumab in moderately to severely active systemic lupus erythematosus: results from two phase III randomized, double-blind, placebo-controlled trials[J]. Arthritis Rheumatol,2017,69(2):362-375.
[12] Day ES,Cachero TG,Qian F,et al.Selectivity of BAFF/BLyS and APRIL for binding to the TNF family receptors BAFFR/BR3 and BCMA[J]. Biochemistry,2005,44(6):1919-1931.
[13] Zheng N,Wang D,Ming H,et al. BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R[J].BMC Nephrol,2015,16:72.
[14] Schwarting A, Relle M, Meineck M, et al. Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse and men[J]. Lupus,2018,27(2):243-256.
[15] Kang S, Fedoriw Y, Brenneman EK.BAFF induces tertiary lymphoid structures and positions T cells within the glomeruli during lupus nephritis[J].J Immunol,2017,198(7):2602-2611.
[16] Nacionales DC,Weinstein JS,Yan XJ,et al. B cell proliferation,somatic hypermutation, class switch recombination,and autoantibody production in ectopic lymphoid tissue in murine lupus[J].J Immunol, 2009,182(7): 4226-4236.
[17] Weinstein JS,Delano MJ,Xu Y,et al. Maintenance of anti-Sm/RNP autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory B cells[J]. J Immunol,2013,190(8): 3916-3927.
[18] Furie R,Stohl W,Ginzler EM,et al.Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus[J]. Arthritis Res Ther,2008,10(5):R109.
[19] Dooley MA,Houssiau F,Aranow C,et al. BLISS-52 and BLISS-76 Study Groups. Effect of belimumab treatment on renal outcomes: Results from the phase 3 belimumab clinical trials in patients with SLE[J]. Lupus,2013,22(1):63-72.
[20] Rovin BH, Dooley MA, Radhakrishnan J,et al. The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized, clinical trials[J].Lupus,2016,25(14):1597-1601.
[21] Lenert A,Niewold TB,Lenert P.Spotlight on blisibimod and its potential in the treatment of systemic lupus erythematosus: evidence to date[J]. Drug Des Devel Ther,2017,11:747-757.
[22] Dall'Era M,Chakravarty E,Wallace D,et al. Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating trial[J].Arthritis Rheum,2007,56(12):4142-4150.
[23] Figgett WA,Deliyanti D,Fairfax KA,et al.Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers[J].J Autoimmun,2015,61:9-16.
[24] Dall'Era M,Davis J.CTLA4Ig: a novel inhibitor of costimulation[J]. Lupu,2004,13(5):372-376.
[25] Wofsy D,Hillson JL,Diamond B.Abatacept for lupus nephritis: alternative definitions of complete responsesupport conflicting conclusions[J]. Arthritis Rheum,2012,64(11):3660-3665.
[26] Furie R,Nicholls K,Cheng TT,et al.Efficacy and safety of abatacept in lupus nephritis a twelve month,randomized,double-blind study[J].Arthritis Rheumatol,2014,66(2):379-389.
[27] Elgueta R,Benson MJ,de Vries VC,et al. Molecular mechanism and function of CD40/CD40L engagement in the immune system[J]. Immunol Rev,2009,229(1):152-172.
[28] Sfikakis PP,Boletis JN,Lionaki S,et al. 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[J]. Arthritis Rheum,2005,52(2): 501-513.
[29] Boumpas DT,Furie R,Manzi S,et al. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreaseshematuria in patients with proliferative lupus glomerulonephritis[J].Arthritis Rheum,2003,48(3): 719-727.
[30] Shock A,Burkly L,Wakefield I,et al.CDP7657,an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study[J]. Arthritis Res Ther,2015,17: 234.
[31] Albach FN,Wagner F, Hüser A,et al.Safety,pharmacokinetics and pharmacodynamics of single rising doses of BI 655064,an antagonistic anti-CD40 antibody in healthy subjects: a potential novel treatment for autoimmune diseases[J]. Eur J Clin Pharmacol,2018,74(2):161-169.