Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis
Arthritis Research & Therapy - 2006
Tóm tắt
The objective of this study was to investigate the interaction between levels of BAFF (B-cell activation factor of the tumour necrosis factor [TNF] family) and APRIL (a proliferation-inducing ligand) and B-cell frequencies in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) treated with the B-cell-depleting agent rituximab. Ten patients with SLE were treated with rituximab in combination with cyclophosphamide and corticosteroids. They were followed longitudinally up to 6 months after B-cell repopulation. Nine patients with RA, resistant or intolerant to anti-TNF therapy, treated with rituximab plus methotrexate were investigated up to 6 months after treatment. The B-cell frequency was determined by flow cytometry, and serum levels of BAFF and APRIL were measured by enzyme-linked immunosorbent assays. BAFF levels rose significantly during B-cell depletion in both patient groups, and in patients with SLE the BAFF levels declined close to pre-treatment levels upon B-cell repopulation. Patients with SLE had normal levels of APRIL at baseline, and during depletion there was a significant decrease. In contrast, patients with RA had APRIL levels 10-fold higher than normal, which did not change during depletion. At baseline, correlations between levels of B cells and APRIL, and DAS28 (disease activity score using 28 joint counts) and BAFF were observed in patients with RA. In summary, increased BAFF levels were observed during absence of circulating B cells in our SLE and RA patient cohorts. In spite of the limited number of patients, our data suggest that BAFF and APRIL are differentially regulated in different autoimmune diseases and, in addition, differently affected by rituximab treatment.
Từ khóa
Tài liệu tham khảo
Eisenberg R: Update on rituximab. Ann Rheum Dis. 2005, 64 (Suppl 4): iv55-57. 10.1136/ard.2005.042648.
Mackay F, Schneider P, Rennert P, Browning J: BAFF and APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003, 21: 231-264. 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: 763-772. 10.1016/j.molimm.2004.06.041.
Schneider P: The role of APRIL and BAFF in lymphocyte activation. Curr Opin Immunol. 2005, 17: 282-289. 10.1016/j.coi.2005.04.005.
Ingold K, Zumsteg A, Tardivel A, Huard B, Steiner QG, Cachero TG, Qiang F, Gorelik L, Kalled SL, Acha-Orbea H, et al: Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med. 2005, 201: 1375-1383. 10.1084/jem.20042309.
Gorelik L, Gilbride K, Dobles M, Kalled SL, Zandman D, Scott ML: Normal B cell homeostasis requires B cell activation factor production by radiation-resistant cells. J Exp Med. 2003, 198: 937-945. 10.1084/jem.20030789.
Dillon SR, Gross JA, Ansell SM, Novak AJ: An APRIL to remember: novel TNF ligands as therapeutic targets. Nat Rev Drug Discov. 2006, 5: 235-246. 10.1038/nrd1982.
Fu L, Lin-Lee YC, Pham LV, Tamayo A, Yoshimura L, Ford RJ: Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas. Blood. 2006, 107: 4540-4548. 10.1182/blood-2005-10-4042.
Novak AJ, Grote DM, Stenson M, Ziesmer SC, Witzig TE, Habermann TM, Harder B, Ristow KM, Bram RJ, Jelinek DF, et al: Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome. Blood. 2004, 104: 2247-2253. 10.1182/blood-2004-02-0762.
He B, Raab-Traub N, Casali P, Cerutti A: EBV-encoded latent membrane protein 1 cooperates with BAFF/BLyS and APRIL to induce T cell-independent Ig heavy chain class switching. J Immunol. 2003, 171: 5215-5224.
He B, Chadburn A, Jou E, Schattner EJ, Knowles DM, Cerutti A: Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. J Immunol. 2004, 172: 3268-3279.
Stohl W, Metyas S, Tan SM, Cheema GS, Oamar B, Xu D, Roschke V, Wu Y, Baker KP, Hilbert DM: B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum. 2003, 48: 3475-3486. 10.1002/art.11354.
Seyler TM, Park YW, Takemura S, Bram RJ, Kurtin PJ, Goronzy JJ, Weyand CM: BLyS and APRIL in rheumatoid arthritis. J Clin Invest. 2005, 115: 3083-3092. 10.1172/JCI25265.
Jonsson MV, Szodoray P, Jellestad S, Jonsson R, Skarstein K: Association between circulating levels of the novel TNF family members APRIL and BAFF and lymphoid organization in primary Sjögren's syndrome. J Clin Immunol. 2005, 25: 189-201. 10.1007/s10875-005-4091-5.
Pers JO, Daridon C, Devauchelle V, Jousse S, Saraux A, Jamin C, Youinou P: BAFF overexpression is associated with autoantibody production in autoimmune diseases. Ann N Y Acad Sci. 2005, 1050: 34-39. 10.1196/annals.1313.004.
Szodoray P, Jonsson R: The BAFF/APRIL system in systemic autoimmune diseases with a special emphasis on Sjögren's syndrome. Scand J Immunol. 2005, 62: 421-428. 10.1111/j.1365-3083.2005.01688.x.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25: 1271-1277.
Vallerskog T, Gunnarsson I, Widhe M, Risselada A, Klareskog L, van Vollenhoven R, Malmstrom V, Trollmo C: Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol.
Cambridge G, Stohl W, Leandro MJ, Migone TS, Hilbert DM, Edwards JC: 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: 723-732. 10.1002/art.21650.
Seror R, Sordet C, Guillevin L, Hachulla E, Masson C, Ittah M, Candon S, Leguern V, Aouba A, Jean S, et al: Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjögren's syndrome. Ann Rheum Dis.
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. 10.1002/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO;2-S.
Groom J, Kalled SL, Cutler AH, Olson C, Woodcock SA, Schneider P, Tschopp J, Cachero TG, Batten M, Wheway J, et al: Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome. J Clin Invest. 2002, 109: 59-68. 10.1172/JCI200214121.
Jacobi AM, Odendahl M, Reiter K, Bruns A, Burmester GR, Radbruch A, Valet G, Lipsky PE, Dorner T: Correlation between circulating CD27high plasma cells and disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 2003, 48: 1332-1342. 10.1002/art.10949.
Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, Brink R, Mackay F, Hodgkin PD, Tangye SG: BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest. 2003, 112: 286-297. 10.1172/JCI200318025.
O'Connor BP, Raman VS, Erickson LD, Cook WJ, Weaver LK, Ahonen C, Lin LL, Mantchev GT, Bram RJ, Noelle RJ: BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004, 199: 91-98. 10.1084/jem.20031330.
Kalled SL: Impact of the BAFF/BR3 axis on B cell survival, germinal center maintenance and antibody production. Semin Immunol. 2006, 18: 290-296. 10.1016/j.smim.2006.06.002.
Stohl W, Metyas S, Tan SM, Cheema GS, Oamar B, Roschke V, Wu Y, Baker KP, Hilbert DM: Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis. 2004, 63: 1096-1103. 10.1136/ard.2003.018663.
Koyama T, Tsukamoto H, Miyagi Y, Himeji D, Otsuka J, Miyagawa H, Harada M, Horiuchi T: Raised serum APRIL levels in patients with systemic lupus erythematosus. Ann Rheum Dis. 2005, 64: 1065-1067. 10.1136/ard.2004.022491.
Tan SM, Xu D, Roschke V, Perry JW, Arkfeld DG, Ehresmann GR, Migone TS, Hilbert DM, Stohl W: Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis. Arthritis Rheum. 2003, 48: 982-992. 10.1002/art.10860.
Ronnblom L, Alm GV: Systemic lupus erythematosus and the type I interferon system. Arthritis Res Ther. 2003, 5: 68-75. 10.1186/ar625.
Beebe AM, Cua DJ, de Waal Malefyt R: The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine Growth Factor Rev. 2002, 13: 403-412. 10.1016/S1359-6101(02)00025-4.
Moreaux J, Cremer FW, Reme T, Raab M, Mahtouk K, Kaukel P, Pantesco V, De Vos J, Jourdan E, Jauch A, et al: The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature. Blood. 2005, 106: 1021-1030. 10.1182/blood-2004-11-4512.
Ohata J, Zvaifler NJ, Nishio M, Boyle DL, Kalled SL, Carson DA, Kipps TJ: 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: 864-870.
Lesley R, Xu Y, Kalled SL, Hess DM, Schwab SR, Shu HB, Cyster JG: Reduced competitiveness of autoantigen-engaged B cells due to increased dependence on BAFF. Immunity. 2004, 20: 441-453. 10.1016/S1074-7613(04)00079-2.
Lavie F, Miceli-Richard C, Ittah M, Sellam J, Gottenberg JE, Mariette X: Increase of B-cell activating factor of the TNF family (BAFF) after rituximab: insights into a new regulating system of BAFF production. Ann Rheum Dis.
Thien M, Phan TG, Gardam S, Amesbury M, Basten A, Mackay F, Brink R: Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity. 2004, 20: 785-798. 10.1016/j.immuni.2004.05.010.
Haiat S, Billard C, Quiney C, Ajchenbaum-Cymbalista F, Kolb JP: Role of BAFF and APRIL in human B-cell chronic lymphocytic leukaemia. Immunology. 2006, 118: 281-292. 10.1111/j.1365-2567.2006.02377.x.
Zintzaras E, Voulgarelis M, Moutsopoulos HM: The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005, 165: 2337-2344. 10.1001/archinte.165.20.2337.
Huard B, Schneider P, Mauri D, Tschopp J, French LE: T cell costimulation by the TNF ligand BAFF. J Immunol. 2001, 167: 6225-6231.