B-cell depletion with rituximab in the treatment of autoimmune diseases: Graves' ophthalmopathy the latest addition to an expanding family

Expert Opinion on Biological Therapy

Volumn 7, Issue 7, 2007, Pages 1061-1078

  Nielsen, Claus H ^a,b   Fassi, Daniel El ^b,c   Hasselbalch, Hans C ^c   Bendtzen, Klaus ^b   Hegedüs, Laszlo ^c  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b Rigshospitalet   (Denmark)

^c ODENSE UNIVERSITY HOSPITAL   (Denmark)

Author keywords

Antigen presenting cells; Autoantibodies; Autoimmunity; B cells; Graves' disease; Graves' ophthalmopathy; Rituximab

Indexed keywords

ANTIHISTAMINIC AGENT; AUTOANTIBODY; CYCLOPHOSPHAMIDE; GLUCOCORTICOID; METHOTREXATE; METHYLPREDNISOLONE SULEPTANATE; PARACETAMOL; PREDNISOLONE; RITUXIMAB; THIAMAZOLE;

AUTOIMMUNE DISEASE; B LYMPHOCYTE; CARCINOGENICITY; DRUG EFFICACY; DRUG MECHANISM; ENDOCRINE OPHTHALMOPATHY; HUMAN; HYPERTHERMIA; HYPOTENSION; INFECTION; INJECTION SITE REACTION; NAUSEA; NONHUMAN; REVIEW; SIDE EFFECT; SYSTEMIC LUPUS ERYTHEMATOSUS;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGEN-PRESENTING CELLS; AUTOANTIBODIES; AUTOIMMUNE DISEASES; B-LYMPHOCYTES; GRAVES DISEASE; GRAVES OPHTHALMOPATHY; HUMANS; IMMUNOGLOBULINS; LYMPHOCYTE DEPLETION; RECEPTORS, THYROTROPIN; T-LYMPHOCYTES;

EID: 34547643406     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.7.7.1061     Document Type: Review

References (144)

1. REFF ME, CARNER K, CHAMBERS KS et al.: Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood (1994) 83:435-445. • The first paper on rituximab, describing the design of the drug and its efficacy in cynomolgus monkeys.
2. BOYE J, ELTER T, ENGERT A: An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab. Ann. Oncol. (2003) 14:520-535.
3. EDWARDS JC, CAMBRIDGE G: Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes. Rheumatology (Oxford) (2001) 40:205-211.
4. COHEN SB, EMERY P, GREENWALD MW et al.: Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, Phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. (2006) 54:2793-2806. • A Phase III trial showing the efficacy of rituximab in anti-TNF-α refractory rheumatoid arthritis.
5. EMERY P, FLEISCHMANN R, FILIPOWICZ-SOSNOWSKA A et al.: The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a Phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum. (2006) 54:1390-1400.
6. COOPER N, STASI R, CUNNINGHAM-RUNDLES S et al.: The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br. J. Haematol. (2004) 125:232-239.
7. ARNOLD DM, DENTALI F, CROWTHER MA et al.: Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann. Intern. Med. (2007) 146:25-33.
8. LOONEY RJ, ANOLIK JH, CAMPBELL D et al.: B cell depletion as a novel treatment for systemic lupus erythematosus: a Phase I/II dose-escalation trial of rituximab. Arthritis Rheum. (2004) 50:2580-2589.
9. VALLERSKOG T, GUNNARSSON I, WIDHE M et al.: Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin. Immunol. (2007) 122:62-74.
10. KEOGH KA, YTTERBERG SR, FERVENZA FC, CARLSON KA, SCHROEDER DR, SPECKS U: Rituximab for refractory Wegener's granulomatosis: report of a prospective, open-label pilot trial. Am. J. Respir. Crit. Care Med. (2006) 173:180-187.
11. STASI R, STIPA E, DEL POETA G, AMADORI S, NEWLAND AC, PROVAN D: Long-term observation of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis treated with rituximab. Rheumatology (Oxford) (2006) 45:1432-1436.
12. PIJPE J, VAN IMHOFF GW, SPIJKERVET FK et al.: Rituximab treatment in patients with primary Sjogren's syndrome: an open-label Phase II study. Arthritis Rheum. (2005) 52:2740-2750.
13. HAIN B, JORDAN K, DESCHAUER M, ZIERZ S: Successful treatment of musk antibody-positive myasthenia gravis with rituximab. Muscle Nerve (2006) 33:575-580.
14. KONG HH, PROSE NS, WARE RE, HALL RP III: Successful treatment of refractory childhood pemphgus vulgaris with anti-CD20 monoclonal antibody (rituximab). Pediatr. Dermato. (2005) 22:461-464.
15. STASI R, BRUNETTI M, STIPA E, AMADORI S: Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia. Blood (2004) 103:4424-4428.
16. GEORGE JN, WOODSON RD, KISS JE, KOJOURI K, VESELY SK: Rituximab therapy for thrombotic thrombocytopenic purpura: a proposed study of the Transfusion Medicine/Hemostasis Clinical Trials Network with a systematic review of rituximab therapy for immune-mediated disorders. J. Clin. Apher. (2006) 21:49-56.
17. EL FASSI D, NIELSEN CH, BONNEMA SJ, HASSELBALCH HC, HEGEDÜS L: B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study. J. Clin. Endocrinol. Metab. (2007) 92(5):1769-1772. •• The first controlled study of rituximabs effect in an autoimmune disorder apart from rheumatoid arthritis. In this trial rituximab therapy did not affect autoantibody levels.
18. EL FASSI D, NIELSEN CH, HASSELBALCH HC, HEGEDÜS L: Treatment-resistant severe, active Graves' ophthalmopathy successfully treated with B lymphocyte depletion. Thyroid (2006) 16:709-710. • A report of successful rituximab therapy in two previously treatment-refractory patients with Graves' ophthalmopathy.
19. SALVI M, VANNUCCHI G, CAMPI I et al.: Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression. Eur. J. Endocrinol. (2006) 154:511-517. • A report describing the absence of B cells from the retrobulbar fat of a patient with Graves' ophthalmopathy following rituximab therapy.
20. SALVI M, VANNUCCHI G, CAMPI I et al.: Treatment of Graves' disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study. Eur. J. Endocrinol. (2007) 156:33-40. •• An open study of rituximabs effect on Graves' ophthalmopathy showing marked clinical responses to therapy.
21. LOKEN MR, SHAH VO, DATTILIO KL, CIVIN CI: Flow cytometric analysis of human bone marrow. II. Normal B lymphocyte development. Blood (1987) 70:1316-1324.
22. STASHENKO P, NADLER LM, HARDY R, SCHLOSSMAN SF: Characterization of a human B lymphocyte-specific antigen. J. Immunol. (1980) 125:1678-1685.
23. DWORZAK MN, FRITSCH G, FLEISCHER C et al.: Multiparameter phenotype mapping of normal and post-chemotherapy B lymphopoiesis in pediatric bone marrow. Leukemia (1997) 11:1266-1273.
24. MCKENNA RW, WASHINGTON LT, AQUINO DB, PICKER LJ, KROFT SH: Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood (2001) 98:2498-2507.
25. LUCIO P, PARREIRA A, VAN DEN BEEMD MW et al.: Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia (1999) 13:419-427.
26. LEANDRO MJ, CAMBRIDGE G, EHRENSTEIN MR, EDWARDS JC: Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum. (2006) 54:613-620.
27. 2+ conductance found constitutively in B lymphocytes. J. Cell Biol. (1993) 121:1121-1132.
28. TEDDER TF, BOYD AW, FREEDMAN AS, NADLER LM, SCHLOSSMAN SF: The B cell surface molecule B1 is functionally linked with B cell activation and differentiation. J. Immunol. (1985) 135:973-979.
29. UCHIDA J, LEE Y, HASEGAWA M et al.: Mouse CD20 expression and function. Int. Immunol. (2004) 16:119-129.
30. DYKSTRA ML, CHERUKURI A, PIERCE SK: Floating the raft hypothesis for immune receptors: access to rafts controls receptor signaling and trafficking. Traffic (2001) 2:160-166.
31. JANAS E, PRIEST R, WILDE JI, WHITE JH, MALHOTRA R: Rituxan (anti-CD20 antibody)-induced translocation of CD20 into lipid rafts is crucial for calcium influx and apoptosis. Clin. Exp. Immunol. (2005) 139:439-446.
32. ANOLIK JH, CAMPBELL D, FELGAR RE et al.: The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum. (2003) 48:455-459.
33. GORTER A, MERI S: Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol. Today (1999) 20:576-582.
34. HARJUNPAA A, JUNNIKKALA S, MERI S: Rituximab (anti-CD20) therapy of B-cell lymphomas: direct complement killing is superior to cellular effector mechanisms. Scand. J. Immunol. (2000) 51:634-641.
35. EDWARDS JC, CAMBRIDGE G: Prospects for B-cell-targeted therapy in autoimmune disease. Rheumatology (Oxford) (2005) 44:151-156.
36. ANOLIK JH, BARNARD J, CAPPIONE A et al.: Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum. (2004) 50:3580-3590.
37. LEANDRO MJ, EDWARDS JC, CAMBRIDGE G: Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion. Ann. Rheum. Dis. (2002) 61:883-888.
38. HAYAKAWA K, HARDY RR: Development and function of B-1 cells. Curr. Opin. Immunol. (2000) 12:346-353.
39. KNEITZ C, WILHELM M, TONY HP: Effective B cell depletion with rituximab in the treatment of autoimmune diseases. Immunobiology (2002) 206:519-527.
40. BOHM I: Increased peripheral blood B-cells expressing the CD5 molecules in association to autoantibodies in patients with lupus erythematosus and evidence to selectively down-modulate them. Biomed. Pharmacother. (2004) 58:338-343.
41. ROUZIERE AS, KNEITZ C, PALANICHAMY A, DORNERT, TONY HP: Regeneration of the immunoglobulin heavy-chain repertoire after transient B-cell depletion with an anti-CD20 antibody. Arthritis Res. Ther. (2005) 7:R714-R724.
42. PUGH-BERNARD AE, SILVERMAN GJ, CAPPIONE AJ et al.: Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance. J. Clin. Invest. (2001) 108:1061-1070.
43. ALWAYN IPJ, XU YX, BASKER M et al.: Effects of specific anti-B and/or anti-plasma cell immunotherapy on antibody production in baboons: depletion of CD20-and CD22-positive B cells does not result in significantly decreased production of anti-α Gal antibody. Xenotransplantation (2001) 8:157-171.
44. SCHRODER C, AZIMZADEH AM, WU G, PRICE JO, ATKINSON JB, PIERSON RN: Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeys. Transpl. Immunol. (2003) 12:19-28.
45. HANSEN S, LESLIE RG: TGN-1412: scrutinizing preclinical trials of antibody-based medicines. Nature (2006) 441:282.
46. GONG Q, OU Q, YE S et al.: Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy. J. Immunol. (2005) 174:817-826.
47. PARAN D, TREJ'O L, CASPI D: Clinical images: B cell depletion in the appendix following rituximab treatment. Arthritis Rheum. (2006) 54:2151.
48. LEANDRO MJ, COOPER N, CAMBRIDGE G, EHRENSTEIN MR, EDWARDS JC: Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy. Rheumatology (Oxford) (2007) 46:29-36.
49. JILANI I, O'BRIEN S, MANSHURI T et al.: Transient down-modulation of CD20 by rituximab in patients with chronic lymphocytic leukemia. Blood (2003) 102:3514-3520.
50. 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. Arthritis Rheum. (2005) 52:501-513.
51. SFIKAKIS PP, SOULIOTIS VL, FRAGIADAKI KG, MOUTSOPOULOS HM, BOLETIS JN, THEOFILOPOULOS AN: Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis. Clin. Immunol. (2007) 123:66-73.
52. SEDDON B, MASON D: Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor β and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC(-) cells and CD4(+)CD8(-) thymocytes. J. Exp. Med. (1999) 189:279-288.
53. VIGNA-PEREZ M, HERNANDEZ-CASTRO B, PAREDES-SAHAROPULOS O 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.
54. TOUBI E, KESSEL A, SLOBODIN G et al.: Macrophage function changes following rituximab treatment in patients with rheumatoid arthritis. Ann. Rheum. Dis. (2006) (In Press).
55. LEVINE TD, PESTRONK A: IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using rituximab. Neurology (1999) 52:1701-1704.
56. ARBUCKLE MR, MCCLAIN MT, RUBERTONE MV et al.: Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. (2003) 349:1526-1533.
57. LEANDRO MJ, EDWARDS JC, CAMBRIDGE G, EHRENSTEIN MR, ISENBERG DA: An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum. (2002) 46:2673-2677.
58. SABAHI R, ANOLIK JH: B-cell-targeted therapy for systemic lupus erythematosus. Drugs (2006) 66:1933-1948.
59. TOKUNAGA M, SAITO K, KAWABATA D et al.: Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann. Rheum. Dis. (2006) 66:470-475.
60. VAN VOLLENHOVEN RF, GUNNARSSON I, WELIN-HENRIKSSON E et al.: Biopsy-verified response of severe lupus nephritis to treatment with rituximab (anti-CD20 monoclonal antibody) plus cyclophosphamide after biopsy-documented failure to respond to cyclophosphamide alone. Scand. J. Rheumatol. (2004) 33:423-427.
61. SMITH KG, JONES RB, BURNS SM, JAYNE DR: Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: remission, relapse, and re-treatment. Arthritis Rheum. (2006) 54:2970-2982.
62. MANDERSON AP, BOTTO M, WALPORT MJ: The role of complement in the development of systemic lupus erythematosus. Ann. Rev. Immunol. (2004) 22:431-456.
63. CINES DB, BLANCHETTE VS: Immune thrombocytopenic purpura. N. Engl. J. Med. (2002) 346:995-1008.
64. EL FASSI D, NIELSEN CH, HASSELBALCH HC, HEGEDÜS L: The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option. Eur. J. Endocrinol. (2006) 154:623-632.
65. HASSELBALCH HC: B-cell depletion with rituximab-a targeted therapy for Graves' disease and autoimmune thyroiditis. Immunol. Lett. (2003) 88:85-86.
66. EDWARDS JC, CAMBRIDGE G, ABRAHAMS VM: Do self-perpetuating B lymphocytes drive human autoimmune disease? Immunology (1999) 97:188-196.
67. ABRAHAMS VM, CAMBRIDGE G, LYDYARD PM, EDWARDS JC: Induction of tumor necrosis factor α production by adhered human monocytes: a key role for Fcγ receptor Type IIIa in rheumatoid arthritis. Arthritis Rheum. (2000) 43:608-616.
68. EDWARDS JC, SZCZEPANSKI L, SZECHINSKI J et al.: Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med (2004) 350:2572-2581. • The first randomized, placebo-controlled trial of rituximab therapy in an autoimmune disease.
69. POPA C, LEANDRO MJ, CAMBRIDGE G, EDWARDS JC: Repeated B lymphocyte depletion with rituximab in rheumatoid arthritis over 7 years. Rheumatology (Oxford) (2006) 46:626-630.
70. DASS S, VITAL EM, EMERY P: Rituximab: novel B-cell depletion therapy for the treatment of rheumatoid arthritis. Expert Opin. Pharmacother. (2006) 7:2559-2570.
71. WEETMAN AP: Graves' disease. N. Engl. J. Med. (2000) 343:1236-1248.
72. ZAKARIJA M, MCKENZIE JM, MUNRO DS: Immunoglobulin G inhibitor of thyroid-stimulating antibody is a cause of delay in the onset of neonatal Graves' disease. J. Clin. Invest. (1983) 72:1352-1356.
73. ASMAN P: Ophthalmological evaluation in thyroid-associated ophthalmopathy. Acta Ophthalmol. Scand. (2003) 81:437-448.
74. WEETMAN AP, MCGREGOR AM, WHEELER MH, HALL R: Extrathyroidal sites of autoantibody synthesis in Graves' disease. Clin. Exp. Immunol. (1984) 56:330-336.
75. CHIOVATO L, LATROFA F, BRAVERMAN LE et al.: Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens. Ann. Intern. Med. (2003) 139:346-351.
76. SMITH TJ, BAHN RS, GORMAN CA: Connective tissue, glycosaminoglycans, and diseases of the thyroid. Endocr. Rev. (1989) 10:366-391.
77. SMITH TJ, WANG HS, EVANS CH: Leukoregulin is a potent inducer of hyaluronan synthesis in cultured human orbital fibroblasts. Am. J. Physiol. (1995) 268:C382-C388.
78. WANG HS, CAO HJ, WINN VD et al.: Leukoregulin induction of prostaglandin-endoperoxide H synthase-2 in human orbital fibroblasts. An in vitro model for connective tissue inflammation. J. Biol. Chem. (1996) 271:22718-22728.
79. YOUNG DA, EVANS CH, SMITH TJ: Leukoregulin induction of protein expression in human orbital fibroblasts: evidence for anatomical site-restricted cytokine-target cell interactions. Proc. Natl. Acad. Sci. USA (1998) 95:8904-8909.
80. WEGROWSKI J, BELLON G, HAYE B, BOREL JP: Effects of thyroid-stimulating hormone and phorbol ester on glycosaminoglycan synthesis in porcine thyroid epithelial cells in primary culture. Cell Biol. Int. Rep. (1989) 13:881-890.
81. ROTELLA CM, ZONEFRATI R, TOCCAFONDI R, VALENTE WA, KOHN LD: Ability of monoclonal antibodies to the thyrotropin receptor to increase collagen synthesis in human fibroblasts: an assay which appears to measure exophthalmogenic immunoglobulins in Graves' sera. J. Clin. Endocrinol. Metab. (1986) 62:357-367.
82. GOPINATH B, MUSSELMAN R, ADAMS CL, TANI J, BEARD N, WALL JR: Study of serum antibodies against three eye muscle antigens and the connective tissue antigen collagen XIII in patients with graves' disease with and without ophthalmopathy: correlation with clinical features. Thyroid (2006) 16:967-974.
83. SMITH TJ, HOA N: Immunoglobulins from patients with Graves' disease induce hyaluronan synthesis in their orbital fibroblasts through the self-antigen, insulin-like growth factor-I receptor. J. Clin. Endocrinol. Metab. (2004) 89:5076-5080.
84. YAMADA M, LI AW, WEST KA, CHANG CH, WALL JR: Experimental model for ophthalmopathy in BALB/c and outbred (CD-1) mice genetically immunized with G2s and the thyrotropin receptor. Autoimmunity (2002) 35:403-413.
85. COOPER DS: Antithyroid drugs. N. Engl J. Med. (2005) 352:905-917.
86. MANCA F, FENOGLIO D, LI PG, KUNKL A, CELADA F: Effect of antigen/antibody ratio on macrophage uptake, processing, and presentation to T cells of antigen complexed with polyclonal antibodies. J. Exp. Med. (1991) 173:37-48.
87. GETAHUN A, DAHLSTROM J, WERNERSSON S, HEYMAN B: IgG2a-mediated enhancement of antibody and T cell responses and its relation to inhibitory and activating Fc γ receptors. J. Immunol. (2004) 172:5269-5276.
88. CAMBRIDGE G, LEANDRO MJ, TEODORESCU M et al.: B cell depletion therapy in systemic lupus erythematosus: effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum. (2006) 54:3612-3622.
89. LOONEY RJ, ANOLIK JH, CAMPBELL D et al.: B cell depletion as a novel treatment for systemic lupus erythematosus - a Phase I/II dose-escalation trial of rituximab. Arthritis Rheum. (2004) 50:2580-2589.
90. GOTTENBERG JE, GUILLEVIN L, LAMBOTTE O et al.: Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann. Rheum. Dis. (2005) 64:913-920.
91. RING T, KALLENBACH M, PRAETORIUS J, NIELSEN S, MELGAARD B: Successful treatment of a patient with primary Sjogren's syndrome with rituximab. Clin. Rheumatol. (2006) 25:891-894.
92. MOSER K, MUEHLINGHAUS G, MANZ R et al.: Long-lived plasma cells in immunity and immunopathology. Immunol. Lett. (2006) 103:83-85.
93. LANZAVECCHIA A: Antigen-specific interaction between T and B cells. Nature (1985) 314:537-539.
94. YANG X, BRUNHAM RC: Gene knockout B cell-deficient mice demonstrate that B cells play an important role in the initiation of T cell responses to Chlamydia trachomatis (mouse pneumonitis) lung infection. J. Immunol. (1998) 161:1439-1446.
95. VORDERMEIER HM, VENKATAPRASAD N, HARRIS DP, IVANYI J: Increase of tuberculous infection in the organs of B cell-deficient mice. Clin. Exp. Immunol. (1996) 106:312-316.
96. MATSUZAKI G, VORDERMEIER HM, HASHIMOTO A, NOMOTO K, IVANYI J: The role of B cells in the establishment of T cell response in mice infected with an intracellular bacteria, Listeria monocytogenes. Cell Immunol. (1999) 194:178-185.
97. CRAWFORD A, MACLEOD M, SCHUMACHER T, CORLETT L, GRAY D: Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J. Immunol. (2006) 176:3498-3506.
98. + T cells. J. Immunol. (1995) 154:4915-4923.
99. HARADA M, MAKINO S: Suppression of overt diabetes in NOD mice by anti-thymocyte serum or anti-Thy 1, 2 antibody. Jikken Dobutsu (1986) 35:501-504.
100. KOIKE T, ITOH Y, ISHII T et al.: Preventive effect of monoclonal anti-L3T4 antibody on development of diabetes in NOD mice. Diabetes (1987) 36:539-541.
101. + T cells. J. Exp. Med. (1987) 166:823-832.
102. + islet-specific T cell clone. Science (1990) 249:1433-1436.
103. SERREZE DV, CHAPMAN HD, VARNUM DS et al.: B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new 'speed congenic' stock of NOD.Igμ null mice. J. Exp. Med. (1996) 184:2049-2053.
104. AKASHI T, NAGAFUCHI S, ANZAI K et al.: Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice. Int. Immunol. (1997) 9:1159-1164.
105. SERREZE DV, FLEMING SA, CHAPMAN HD, RICHARD SD, LEITER EH, TISCH RM: B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice. J. Immunol. (1998) 161:3912-3918.
106. TAKEMURA S, KLIMIUK PA, BRAUN A, GORONZY JJ, WEYAND CM: T cell activation in rheumatoid synovium is B cell dependent. J. Immunol. (2001) 167:4710-4718. • A paper describing the importance of B cells in the pathogenesis of rheumatoid arthritis. Severe combined immunodeficiency mice implanted with human rheumatoid synovium were subjected to rituximab therapy.
107. 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.
108. GUO J, WANG Y, RAPOPORT B, MCLACHLAN SM: Evidence for antigen presentation to sensitized T cells by thyroid peroxidase (TPO)-specific B cells in mice injected with fibroblasts co-expressing TPO and MHC class II. Clin. Exp. Immunol. (2000) 119:38-46.
109. PICHURIN P, ALIESKY H, CHEN CR, NAGAYAMA Y, RAPOPORT B, MCLACHLAN SM: Thyrotrophin receptor-specific memory T cell responses require normal B cells in a murine model of Graves' disease. Clin. Exp. Immunol. (2003) 134:396-402.
110. BRALEY-MULLEN H, YU S: Early requirement for B cells for development of spontaneous autoimmune thyroiditis in NOD.H-2h4 mice. J. Immunol. (2000) 165:7262-7269.
111. STORCH MK, PIDDLESDEN S, HALTIA M, IIVANAINEN M, MORGAN P, LASSMANN H: Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination. Ann. Neurol. (1998) 43:465-471.
112. TRAN GT, HODGKINSON SJ, CARTER N, KILLINGSWORTH M, SPICER ST, HALL BM: Attenuation of experimental allergic encephalomyelitis in complement component 6-deficient rats is associated with reduced complement C9 deposition, P-selectin expression, and cellular infiltrate in spinal cords. J. Immunol. (2002) 168:4293-4300.
113. SOSPEDRA M, MARTIN R: Immunology of multiple sclerosis. Ann. Rev. Immunol. (2005) 23:683-747.
114. BERGER T, RUBNER P, SCHAUTZER F et al.: Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl. J. Med. (2003) 349:139-145.
115. GIANANI R, EISENBARTH GS: The stages of Type 1A diabetes: 2005. Immunol. Rev. (2005) 204:232-249.
116. NIELSEN CH, LESLIE RG, JEPSEN BS, KAZATCHKINE MD, KAVERI SV, FISCHER E: Natural autoantibodies and complement promote the uptake of a self antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4(+) T cells in healthy individuals. Eur. J. Immunol. (2001) 31:2660-2668.
117. + T cell proliferation in response to self antigens. Eur. J. Immunol. (2004) 34:263-272.
118. THORNTON BP, VETVICKA V, ROSS GD: Natural antibody and complement-mediated antigen processing and presentation by B lymphocytes. J. Immunol. (1994) 152:1727-1737.
119. THORNTON BP, VETVICKA V, ROSS GD: Function of C3 in a humoral response: iC3b/C3dg bound to an immune complex generated with natural antibody and a primary antigen promotes antigen uptake and the expression of co-stimulatory molecules by all B cells, but only stimulates immunoglobulin synthesis by antigen-specific B cells. Clin. Exp. Immunol. (1996) 104:531-537.
120. NIELSEN CH, LESLIE RG: Complement's participation in acquired immunity. J. Leukoc. Biol. (2002) 72:249-261.
121. ARVIEUX J, YSSEL H, COLOMB MG: Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones. Immunology (1988) 65:229-235.
122. JACQUIER-SARLIN MR, GABERT FM, VILLIERS MB, COLOMB MG: Modulation of antigen processing and presentation by covalently linked complement C3b fragment. Immunology (1995) 84:164-170.
123. BOACKLE SA, MORRIS MA, HOLERS VM, KARP DR: Complement opsonization is required for presentation of immune complexes by resting peripheral blood B cells. J. Immunol. (1998) 161:6537-6543.
124. KORB LC, AHEARN JM: C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J. Immunol. (1997) 158:4525-4528.
125. OCHSENBEIN AF, FEHR T, LUTZ C et al.: Control of early viral and bacterial distribution and disease by natural antibodies. Science (1999) 286:2156-2159.
126. KIMBY E: Tolerability and safety of rituximab (MabThera). Cancer Treat. Rev. (2005) 31:456-473.
127. JENSEN M, WINKLER U, MANZKE O, DIEHL V, ENGERT A: Rapid tumor lysis in a patient with B-cell chronic lymphocytic leukemia and lymphocytosis treated with an anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab). Ann. Hematol. (1998) 77:89-91.
128. GUTIERREZ A, RODRIGUEZ J, MARTINEZ J et al.: Pathogenic study of anti-CD20 infusion-related severe refractory shock in diffuse large B-cell lymphoma. Leuk. Lymphoma (2006) 47:111-115.
129. BENDTZEN K, GEBOREK P, SVENSON M, LARSSON L, KAPETANOVIC MC, SAXNE T: Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor a inhibitor infliximab. Arthritis Rheum. (2006) 54:3782-3789.
130. ANDERSON D, BISHOP JB, GARNER RC, OSTROSKY-WEGMAN P, SELBY PB: Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat. Res. (1995) 330:115-181.
131. SMELAND EB, BLOMHOFF HK, FUNDERUD S, SHALABY MR, ESPEVIK T: Interleukin 4 induces selective production of interleukin 6 from normal human B lymphocytes. J. Exp. Med. (1989) 170:1463-1468.
132. FILLATREAU S, SWEENIE CH, MCGEACHY MJ, GRAY D, ANDERTON SM: B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. (2002) 3:944-950.
133. MAURI C, GRAY D, MUSHTAQ N, LONDEI M: Prevention of arthritis by interleukin 10-producing B cells. J. Exp. Med (2003) 197:489-501.
134. + T cells: role of TGF-β 1. J. Immunol. (2003) 170:5897-5911.
135. BENNETT SR, CARBONE FR, TOY T, MILLER JF, HEATH WR: B cells directly tolerize CD8(+) T cells. J. Exp. Med. (1998) 188:1977-1983.
136. H1 development. J. Immunol. (1999) 163:4284-4291.
137. BOURKE E, BOSISIO D, GOLAY J, POLENTARUTTI N, MANTOVANI A: The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Blood (2003) 102:956-963.
138. CHRISTENSEN SR, KASHGARIAN M, ALEXOPOULOU L, FLAVELL RA, AKIRA S, SHLOMCHIK MJ: Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J. Exp. Med. (2005) 202:321-331.
139. CHRISTENSEN SR, SHUPE J, NICKERSON K, KASHGARIAN M, FLAVELL RA, SHLOMCHIK MJ: Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity (2006) 25:417-428.
140. CARELLA C, MAZZIOTTI G, SORVILLO F et al.: Serum thyrotropin receptor antibodies concentrations in patients with Graves' disease before, at the end of methimazole treatment, and after drug withdrawal: evidence that the activity of thyrotropin receptor antibody and/or thyroid response modify during the observation period. Thyroid (2006) 16:295-302.
141. BROWNING JL: B cells move to centre stage: novel opportunities for autoimmune disease treatment. Nat. Rev. Drug Discov. (2006) 5:564-576.
142. GILBERT JA, KALLED SL, MOORHEAD J et al.: Treatment of autoimmune hyperthyroidism in a murine model of Graves' disease with tumor necrosis factor-family ligand inhibitors suggests a key role for B cell activating factor in disease pathology. Endocrinology (2006) 147:4561-4568. • The first description of a B-cell specific therapy in a murine model of Graves' disease.
143. CAWOOD T, MORIARTY P, O'SHEA D: Recent developments in thyroid eye disease. Br. Med. J. (2004) 329:385-390.
144. EL FASSI D, NIELSEN CH, BENDTZEN K: Rituximab (MabThera) as treatment of active rheumatoid arthritis. Ugeskr. Laeger (2006) 168:4079-4081.