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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 5/2012

01-11-2012 | Review

Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity

Authors: Henrik E Mei, Stefanie Schmidt, Thomas Dörner

Published in: Arthritis Research & Therapy | Special Issue 5/2012

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Abstract

Anti-CD20 therapy using rituximab directly targeting B cells has been approved for treatment of non-Hodgkin lymphoma, rheumatoid arthritis and anti-neutrophil cytoplasmic antibody-associated vasculitides and has led to reappreciation of B-lineage cells for anti-rheumatic treatment strategies. Moreover, blocking B-cell activating factor with belimumab, a drug that is licensed for treatment of active, seropositive systemic lupus erythematosus (SLE), represents an alternative, indirect anti-B-cell approach interfering with proper B-cell development. While these approaches apparently have no substantial impact on antibody-secreting plasma cells, challenges to improve the treatment of difficult-to-treat patients with SLE remain. In this context, anti-CD19 antibodies have the promise to directly target autoantibody-secreting plasmablasts and plasma cells as well as early B-cell differentiation stages not covered by anti-CD20 therapy. Currently known distinct expression profiles of CD19 by human plasma cell subsets, experiences with anti-CD19 therapies in malignant conditions as well as the rationale of targeting autoreactive plasma cells in patients with SLE are discussed in this review.
Literature
1.
Edwards JC, Cambridge G: B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol. 2006, 6: 394-403. 10.1038/nri1838.PubMed
2.
Dorner T: SLE in 2011: deciphering the role of NETs and networks in SLE. Nat Rev Rheumatol. 2012, 8: 68-70.PubMed
3.
Hiepe F, Dorner T, Hauser AE, Hoyer BF, Mei H, Radbruch A: Long-lived autoreactive plasma cells drive persistent autoimmune inflammation. Nat Rev Rheumatol. 2011, 7: 170-178. 10.1038/nrrheum.2011.1.PubMed
4.
Reininger L, Radaszkiewicz T, Kosco M, Melchers F, Rolink AG: Development of autoimmune disease in SCID mice populated with long-term 'in vitro' proliferating (NZB × NZW)F1 pre-B cells. J Exp Med. 1992, 176: 1343-1353. 10.1084/jem.176.5.1343.PubMed
5.
Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S, Mei H, Radtke H, Gromnica-Ihle E, Burmester GR, Arnold R, Radbruch A, Hiepe F: Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood. 2009, 113: 214-223. 10.1182/blood-2008-07-168286.PubMed
6.
Dorner T, Radbruch A, Burmester GR: B-cell-directed therapies for autoimmune disease. Nat Rev Rheumatol. 2009, 5: 433-441. 10.1038/nrrheum.2009.141.PubMed
7.
Yoshida T, Mei H, Dorner T, Hiepe F, Radbruch A, Fillatreau S, Hoyer BF: Memory B and memory plasma cells. Immunol Rev. 2010, 237: 117-139. 10.1111/j.1600-065X.2010.00938.x.PubMed
8.
Cassese G, Arce S, Hauser AE, Lehnert K, Moewes B, Mostarac M, Muehlinghaus G, Szyska M, Radbruch A, Manz RA: Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J Immunol. 2003, 171: 1684-1690.PubMed
9.
Tangye SG: Staying alive: regulation of plasma cell survival. Trends Immunol. 2011, 32: 595-602. 10.1016/j.it.2011.09.001.PubMed
10.
Stohl W, Scholz JL, Cancro MP: Targeting BLyS in rheumatic disease: the sometimes-bumpy road from bench to bedside. Curr Opin Rheumatol. 2011, 23: 305-310. 10.1097/BOR.0b013e328344c15e.PubMedCentralPubMed
11.
Benson MJ, Dillon SR, Castigli E, Geha RS, Xu S, Lam KP, Noelle RJ: Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFFand APRIL. J Immunol. 2008, 180: 3655-3659.PubMed
12.
Dall'Era M, Chakravarty E, Wallace D, Genovese M, Weisman M, Kavanaugh A, Kalunian K, Dhar P, Vincent E, Pena-Rossi C, Wofsy D : Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, doubleblind, placebo-controlled, dose-escalating trial. Arthritis Rheum. 2007, 56: 4142-4150. 10.1002/art.23047.PubMed
13.
Genovese MC, Kinnman N, de La Bourdonnaye G, Pena Rossi C, Tak PP: 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: 1793-1803. 10.1002/art.30373.PubMed
14.
Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, Leon MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA : Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011, 377: 721-731. 10.1016/S0140-6736(10)61354-2.PubMed
15.
Geffroy-Luseau A, Jego G, Bataille R, Campion L, Pellat-Deceunynck C: Osteoclasts support the survival of human plasma cells in vitro. Int Immunol. 2008, 20: 775-782. 10.1093/intimm/dxn035.PubMed
16.
Jacobi AM, Huang W, Wang T, Freimuth W, Sanz I, Furie R, Mackay M, Aranow C, Diamond B, Davidson A: Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, doubleblind, placebo-controlled, dose-ranging study. Arthritis Rheum. 2010, 62: 201-210. 10.1002/art.27189.PubMedCentralPubMed
17.
Teng YK, Levarht EW, Hashemi M, Bajema IM, Toes RE, Huizinga TW, van Laar JM: Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment. Arthritis Rheum. 2007, 56: 3909-3918. 10.1002/art.22967.PubMed
18.
Rehnberg M, Amu S, Tarkowski A, Bokarewa MI, Brisslert M: Short- and long-term effects of anti-CD20 treatment on B cell ontogeny in bone marrow of patients with rheumatoid arthritis. Arthritis Res Ther. 2009, 11: R123-10.1186/ar2789.PubMedCentralPubMed
19.
Mei HE, Frolich D, Giesecke C, Loddenkemper C, Reiter K, Schmidt S, Feist E, Daridon C, Tony HP, Radbruch A, Dorner T: Steady state generation of mucosal IgA+ plasmablasts is not abrogated by B cell depletion therapy with rituximab. Blood. 2010, 116: 5181-5190. 10.1182/blood-2010-01-266536.PubMed
20.
Cambridge G, Leandro MJ, Edwards JC, Ehrenstein MR, Salden M, Bodman-Smith M, Webster AD: Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum. 2003, 48: 2146-2154. 10.1002/art.11181.PubMed
21.
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. 2007, 122: 62-74. 10.1016/j.clim.2006.08.016.PubMed
22.
Stohl W, Gomez-Reino J, Olech E, Dudler J, Fleischmann RM, Zerbini CA, Ashrafzadeh A, Grzeschik S, Bieraugel R, Green J, Francom S, Dummer W: Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial. Ann Rheum Dis. 2012, 71: 1289-1296. 10.1136/annrheumdis-2011-200706.PubMedCentralPubMed
23.
Pisetsky DS, Grammer AC, Ning TC, Lipsky PE: Are autoantibodies the targets of B-cell-directed therapy?. Nat Rev Rheumatol. 2011, 7: 551-556. 10.1038/nrrheum.2011.108.PubMed
24.
Kunkel EJ, Butcher EC: Plasma-cell homing. Nat Rev Immunol. 2003, 3: 822-829. 10.1038/nri1203.PubMed
25.
Mei HE, Yoshida T, Sime W, Hiepe F, Thiele K, Manz RA, Radbruch A, Dorner T: Blood-borne human plasma cells in steady state are derived from mucosal immune responses. Blood. 2009, 113: 2461-2469. 10.1182/blood-2008-04-153544.PubMed
26.
Shapiro-Shelef M, Calame K: Regulation of plasma-cell development. Nat Rev Immunol. 2005, 5: 230-242. 10.1038/nri1572.PubMed
27.
Oracki SA, Walker JA, Hibbs ML, Corcoran LM, Tarlinton DM: Plasma cell development and survival. Immunol Rev. 2010, 237: 140-159. 10.1111/j.1600-065X.2010.00940.x.PubMed
28.
Benner R, Hijmans W, Haaijman JJ: The bone marrow: the major source of serum immunoglobulins, but still a neglected site of antibody formation. Clin Exp Immunol. 1981, 46: 1-8.PubMedCentralPubMed
29.
McMillan R, Longmire RL, Yelenosky R, Lang JE, Heath V, Craddock CG: Immunoglobulin synthesis by human lymphoid tissues: normal bone marrow as a major site of IgG production. J Immunol. 1972, 109: 1386-1394.PubMed
30.
Manz RA, Thiel A, Radbruch A: Lifetime of plasma cells in the bone marrow. Nature. 1997, 388: 133-134. 10.1038/40540.PubMed
31.
Slifka MK, Antia R, Whitmire JK, Ahmed R: Humoral immunity due to longlived plasma cells. Immunity. 1998, 8: 363-372. 10.1016/S1074-7613(00)80541-5.PubMed
32.
Amanna IJ, Carlson NE, Slifka MK: Duration of humoral immunity to common viral and vaccine antigens. N Engl J Med. 2007, 357: 1903-1915. 10.1056/NEJMoa066092.PubMed
33.
Manz RA, Hauser AE, Hiepe F, Radbruch A: Maintenance of serum antibody levels. Annu Rev Immunol. 2005, 23: 367-386. 10.1146/annurev.immunol.23.021704.115723.PubMed
34.
Hoyer BF, Moser K, Hauser AE, Peddinghaus A, Voigt C, Eilat D, Radbruch A, Hiepe F, Manz RA: Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. J Exp Med. 2004, 199: 1577-1584. 10.1084/jem.20040168.PubMedCentralPubMed
35.
Cambridge G, Isenberg DA, Edwards JC, Leandro MJ, Migone TS, Teodorescu M, Stohl W: B cell depletion therapy in systemic lupus erythematosus: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response. Ann Rheum Dis. 2008, 67: 1011-1016.PubMed
36.
Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KG, Dorner T, Hiepe F: Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol. 2006, 6: 741-750. 10.1038/nri1886.PubMed
37.
Miller JJ, Cole LJ: Resistance of long-lived lymphocytes and plasma cells in rat lymph nodes to treatment with prednisone, cyclophosphamide, 6-mercaptopurine, and actinomycin D. J Exp Med. 1967, 126: 109-125. 10.1084/jem.126.1.109.PubMedCentralPubMed
38.
Roldan E, Brieva JA: Terminal differentiation of human bone marrow cells capable of spontaneous and high-rate immunoglobulin secretion: role of bone marrow stromal cells and interleukin 6. Eur J Immunol. 1991, 21: 2671-2677. 10.1002/eji.1830211105.PubMed
39.
Pelletier N, Casamayor-Palleja M, De Luca K, Mondiere P, Saltel F, Jurdic P, Bella C, Genestier L, Defrance T: The endoplasmic reticulum is a key component of the plasma cell death pathway. J Immunol. 2006, 176: 1340-1347.PubMed
40.
Hofer T, Muehlinghaus G, Moser K, Yoshida T, Mei HE, Hebel K, Hauser A, Hoyer B, E OL, Dorner T, Manz RA, Hiepe F, Radbruch A: Adaptation of humoral memory. Immunol Rev. 2006, 211: 295-302. 10.1111/j.0105-2896.2006.00380.x.PubMed
41.
Mohr E, Serre K, Manz RA, Cunningham AF, Khan M, Hardie DL, Bird R, MacLennan IC: Dendritic cells and monocyte/macrophages that create the IL-6/APRIL-rich lymph node microenvironments where plasmablasts mature. J Immunol. 2009, 182: 2113-2123. 10.4049/jimmunol.0802771.PubMed
42.
Minges Wols HA, Underhill GH, Kansas GS, Witte PL: The role of bone marrow-derived stromal cells in the maintenance of plasma cell longevity. J Immunol. 2002, 169: 4213-4221.PubMed
43.
Tokoyoda K, Egawa T, Sugiyama T, Choi BI, Nagasawa T: Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004, 20: 707-718. 10.1016/j.immuni.2004.05.001.PubMed
44.
Chu VT, Frohlich A, Steinhauser G, Scheel T, Roch T, Fillatreau S, Lee JJ, Lohning M, Berek C: Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol. 2011, 12: 151-159.PubMed
45.
Matthes T, Dunand-Sauthier I, Santiago-Raber ML, Krause KH, Donze O, Passweg J, McKee T, Huard B: Production of the plasma-cell survival factor a proliferation-inducing ligand (APRIL) peaks in myeloid precursor cells from human bone marrow. Blood. 2011, 118: 1838-1844. 10.1182/blood-2011-01-332940.PubMed
46.
Winter O, Moser K, Mohr E, Zotos D, Kaminski H, Szyska M, Roth K, Wong DM, Dame C, Tarlinton DM, Schulze H, MacLennan IC, Manz RA: Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow. Blood. 2010, 116: 1867-1875. 10.1182/blood-2009-12-259457.PubMed
47.
Rozanski CH, Arens R, Carlson LM, Nair J, Boise LH, Chanan-Khan AA, Schoenberger SP, Lee KP: Sustained antibody responses depend on CD28 function in bone marrow-resident plasma cells. J Exp Med. 2011, 208: 1435-1446. 10.1084/jem.20110040.PubMedCentralPubMed
48.
Rodriguez Gomez M, Talke Y, Goebel N, Hermann F, Reich B, Mack M: Basophils support the survival of plasma cells in mice. J Immunol. 2010, 185: 7180-7185. 10.4049/jimmunol.1002319.PubMed
49.
Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, Schneider P, Huard B, Lambert PH, Siegrist CA: APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells. Blood. 2008, 111: 2755-2764. 10.1182/blood-2007-09-110858.PubMed
50.
Moser K, Tokoyoda K, Radbruch A, MacLennan I, Manz RA: Stromal niches, plasma cell differentiation and survival. Curr Opin Immunol. 2006, 18: 265-270. 10.1016/j.coi.2006.03.004.PubMed
51.
Xiang Z, Cutler AJ, Brownlie RJ, Fairfax K, Lawlor KE, Severinson E, Walker EU, Manz RA, Tarlinton DM, Smith KG: FcγRIIb controls bone marrow plasma cell persistence and apoptosis. Nat Immunol. 2007, 8: 419-429. 10.1038/ni1440.PubMed
52.
Hutloff A, Buchner K, Reiter K, Baelde HJ, Odendahl M, Jacobi A, Dorner T, Kroczek RA: Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus. Arthritis Rheum. 2004, 50: 3211-3220. 10.1002/art.20519.PubMed
53.
Cassese G, Lindenau S, de Boer B, Arce S, Hauser A, Riemekasten G, Berek C, Hiepe F, Krenn V, Radbruch A, Manz RA: Inflamed kidneys of NZB/W mice are a major site for the homeostasis of plasma cells. Eur J Immunol. 2001, 31: 2726-2732. 10.1002/1521-4141(200109)31:9<2726::AID-IMMU2726>3.0.CO;2-H.PubMed
54.
Jacobi AM, Mei H, Hoyer BF, Mumtaz IM, Thiele K, Radbruch AH, Burmester GR, Hiepe F, Dorner T: HLA-DRhigh/CD27high plasmablasts indicate active disease in patients with SLE. Ann Rheum Dis. 2010, 69: 305-308. 10.1136/ard.2008.096495.PubMed
55.
Bijl M, Horst G, Bootsma H, Limburg PC, Kallenberg CG: Mycophenolate mofetil prevents a clinical relapse in patients with systemic lupus erythematosus at risk. Ann Rheum Dis. 2003, 62: 534-539. 10.1136/ard.62.6.534.PubMedCentralPubMed
56.
Neubert K, Meister S, Moser K, Weisel F, Maseda D, Amann K, Wiethe C, Winkler TH, Kalden JR, Manz RA, Voll RE: The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat Med. 2008, 14: 748-755. 10.1038/nm1763.PubMed
57.
Frohlich K, Holle JU, Aries PM, Gross WL, Moosig F: Successful use of bortezomib in a patient with systemic lupus erythematosus and multiple myeloma. Ann Rheum Dis. 2011, 70: 1344-1345. 10.1136/ard.2010.133256.PubMed
58.
Haas KM, Tedder TF: Role of the CD19 and CD21/35 receptor complex in innate immunity, host defense and autoimmunity. Adv Exp Med Biol. 2005, 560: 125-139. 10.1007/0-387-24180-9_16.PubMed
59.
Kozmik Z, Wang S, Dorfler P, Adams B, Busslinger M: The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP. Mol Cell Biol. 1992, 12: 2662-2672.PubMedCentralPubMed
60.
Cabanillas F, Burke JS, Smith TL, Moon TE, Butler JJ, Rodriguez V: Factors predicting for response and survival in adults with advanced non-Hodgkin's lymphoma. Arch Intern Med. 1978, 138: 413-418. 10.1001/archinte.1978.03630270051019.PubMed
61.
Nutt SL, Morrison AM, Dorfler P, Rolink A, Busslinger M: Identification of BSAP (Pax-5) target genes in early B-cell development by loss- and gain-of-function experiments. Embo J. 1998, 17: 2319-2333. 10.1093/emboj/17.8.2319.PubMedCentralPubMed
62.
Nutt SL, Heavey B, Rolink AG, Busslinger M: Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature. 1999, 401: 556-562. 10.1038/44076.PubMed
63.
Cobaleda C, Schebesta A, Delogu A, Busslinger M: Pax5: the guardian of B cell identity and function. Nat Immunol. 2007, 8: 463-470. 10.1038/ni1454.PubMed
64.
Scheuermann RH, Racila E: CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995, 18: 385-397. 10.3109/10428199509059636.PubMed
65.
Nadler LM, Anderson KC, Marti G, Bates M, Park E, Daley JF, Schlossman SF: B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes. J Immunol. 1983, 131: 244-250.PubMed
66.
Anderson KC, Griffin JD, Bates MP, Slaughenhoupt BL, Schlossman SF, Nadler LM: Isolation and characterization of human B lymphocyte enriched populations. I. Purification of B cells by immune rosette depletion. J Immunol Methods. 1983, 61: 283-292. 10.1016/0022-1759(83)90222-3.PubMed
67.
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.PubMed
68.
Maecker HT, Levy S: Normal lymphocyte development but delayed humoral immune response in CD81-null mice. J Exp Med. 1997, 185: 1505-1510. 10.1084/jem.185.8.1505.PubMedCentralPubMed
69.
van Zelm MC, Smet J, Adams B, Mascart F, Schandene L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M: CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest. 2010, 120: 1265-1274. 10.1172/JCI39748.PubMedCentralPubMed
70.
Dobbs AK, Bosompem A, Coustan-Smith E, Tyerman G, Saulsbury FT, Conley ME: Agammaglobulinemia associated with BCR B cells and enhanced expression of CD19. Blood. 2011, 118: 1828-1837. 10.1182/blood-2011-01-330472.PubMedCentralPubMed
71.
Artac H, Reisli I, Kara R, Pico-Knijnenburg I, Adin-Cinar S, Pekcan S, Jol-van der Zijde CM, van Tol MJ, Bakker-Jonges LE, van Dongen JJ, van der Burg M, van Zelm MC: B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele. Genes Immun. 2010, 11: 523-530. 10.1038/gene.2010.22.PubMed
72.
van Zelm MC, Reisli I, van der Burg M, Castano D, van Noesel CJ, van Tol MJ, Woellner C, Grimbacher B, Patino PJ, van Dongen JJ, Franco JL: An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med. 2006, 354: 1901-1912. 10.1056/NEJMoa051568.PubMed
73.
Sato S, Hasegawa M, Fujimoto M, Tedder TF, Takehara K: Quantitative genetic variation in CD19 expression correlates with autoimmunity. J Immunol. 2000, 165: 6635-6643.PubMed
74.
Fearon DT, Carroll MC: Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu Rev Immunol. 2000, 18: 393-422. 10.1146/annurev.immunol.18.1.393.PubMed
75.
Engel P, Zhou LJ, Ord DC, Sato S, Koller B, Tedder TF: Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity. 1995, 3: 39-50. 10.1016/1074-7613(95)90157-4.PubMed
76.
Rickert RC, Rajewsky K, Roes J: Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature. 1995, 376: 352-355. 10.1038/376352a0.PubMed
77.
Inaoki M, Sato S, Weintraub BC, Goodnow CC, Tedder TF: CD19-regulated signaling thresholds control peripheral tolerance and autoantibody production in B lymphocytes. J Exp Med. 1997, 186: 1923-1931. 10.1084/jem.186.11.1923.PubMedCentralPubMed
78.
Mahmoud MS, Fujii R, Ishikawa H, Kawano MM: Enforced CD19 expression leads to growth inhibition and reduced tumorigenicity. Blood. 1999, 94: 3551-3558.PubMed
79.
Culton DA, Nicholas MW, Bunch DO, Zhen QL, Kepler TB, Dooley MA, Mohan C, Nachman PH, Clarke SH: Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. J Clin Immunol. 2007, 27: 53-68. 10.1007/s10875-006-9051-1.PubMed
80.
Korganow AS, Knapp AM, Nehme-Schuster H, Soulas-Sprauel P, Poindron V, Pasquali JL, Martin T: Peripheral B cell abnormalities in patients with systemic lupus erythematosus in quiescent phase: decreased memory B cells and membrane CD19 expression. J Autoimmun. 2010, 34: 426-434. 10.1016/j.jaut.2009.11.002.PubMed
81.
Sato S, Fujimoto M, Hasegawa M, Takehara K: Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells. Arthritis Rheum. 2004, 50: 1918-1927. 10.1002/art.20274.PubMed
82.
Odendahl M, Keitzer R, Wahn U, Hiepe F, Radbruch A, Dorner T, Bunikowski R: Perturbations of peripheral B lymphocyte homoeostasis in children with systemic lupus erythematosus. Ann Rheum Dis. 2003, 62: 851-858. 10.1136/ard.62.9.851.PubMedCentralPubMed
83.
Odendahl M, Mei H, Hoyer BF, Jacobi AM, Hansen A, Muehlinghaus G, Berek C, Hiepe F, Manz R, Radbruch A, Dorner T: Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. Blood. 2005, 105: 1614-1621. 10.1182/blood-2004-07-2507.PubMed
84.
Odendahl M, Jacobi A, Hansen A, Feist E, Hiepe F, Burmester GR, Lip sky PE, Radbruch A, Dorner T: Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J Immunol. 2000, 165: 5970-5979.PubMed
85.
Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Catovsky D: Levels of expression of CD19 and CD20 in chronic B cell leukaemias. J Clin Pathol. 1998, 51: 364-369. 10.1136/jcp.51.5.364.PubMedCentralPubMed
86.
Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M, Woods R, Rowe DC, Cheng L, Cook K, Evans K, Sims GP, Pfarr DS, Bowen MA, Dall'Acqua W, Shlomchik M, Tedder TF, Kiener P, Jallal B, Wu H, Coyle AJ: B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010, 335: 213-222. 10.1124/jpet.110.168062.PubMed
87.
Horton HM, Bernett MJ, Pong E, Peipp M, Karki S, Chu SY, Richards J O, Vostiar I, Joyce PF, Repp R, Desjarlais JR, Zhukovsky EA: Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res. 2008, 68: 8049-8057. 10.1158/0008-5472.CAN-08-2268.PubMed
88.
Nicholas MW, Dooley MA, Hogan SL, Anolik J, Looney J, Sanz I, Clarke SH: A novel subset of memory B cells is enriched in autoreactivity and correlates with adverse outcomes in SLE. Clin Immunol. 2008, 126: 189-201. 10.1016/j.clim.2007.10.004.PubMedCentralPubMed
89.
Wehr C, Eibel H, Masilamani M, Illges H, Schlesier M, Peter HH, Warnatz K: A new CD21low B cell population in the peripheral blood of patients with SLE. Clin Immunol. 2004, 113: 161-171. 10.1016/j.clim.2004.05.010.PubMed
90.
Huggins J, Pellegrin T, Felgar RE, Wei C, Brown M, Zheng B, Milner EC, Bernstein SH, Sanz I, Zand MS: CpG DNA activation and plasma-cell differentiation of CD27-naive human B cells. Blood. 2007, 109: 1611-1619. 10.1182/blood-2006-03-008441.PubMedCentralPubMed
91.
92.
Warnatz K, Wehr C, Drager R, Schmidt S, Eibel H, Schlesier M, Peter HH: Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology. 2002, 206: 502-513. 10.1078/0171-2985-00198.PubMed
93.
Trepel F: Number and distribution of lymphocytes in man. A critical analysis. Klin Wochenschr. 1974, 52: 511-515. 10.1007/BF01468720.PubMed
94.
Westermann J, Pabst R: Lymphocyte subsets in the blood: a diagnostic window on the lymphoid system?. Immunol Today. 1990, 11: 406-410.PubMed
95.
Ellyard JI, Avery DT, Phan TG, Hare NJ, Hodgkin PD, Tangye SG: Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow. Blood. 2004, 103: 3805-3812. 10.1182/blood-2003-09-3109.PubMed
96.
Medina F, Segundo C, Campos-Caro A, Gonzalez-Garcia I, Brieva JA: The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression. Blood. 2002, 99: 2154-2161. 10.1182/blood.V99.6.2154.PubMed
97.
Withers DR, Fiorini C, Fischer RT, Ettinger R, Lipsky PE, Grammer A C: T cell-dependent survival of CD20+ and CD20- plasma cells in human secondary lymphoid tissue. Blood. 2007, 109: 4856-4864. 10.1182/blood-2006-08-043414.PubMedCentralPubMed
98.
Arce S, Luger E, Muehlinghaus G, Cassese G, Hauser A, Horst A, Lehnert K, Odendahl M, Honemann D, Heller KD, Kleinschmidt H, Berek C, Dorner T, Krenn V, Hiepe F, Bargou R, Radbruch A, Manz RA: CD38low IgG-secreting cells are precursors of various CD38high-expressing plasma cell populations. J Leukoc Biol. 2004, 75: 1022-1028. 10.1189/jlb.0603279.PubMed
99.
Harada H, Kawano MM, Huang N, Harada Y, Iwato K, Tanabe O, Tanaka H, Sakai A, Asaoku H, Kuramoto A: Phenotypic difference of normal plasma cells from mature myeloma cells. Blood. 1993, 81: 2658-2663.PubMed
100.
Kallies A, Hasbold J, Tarlinton DM, Dietrich W, Corcoran LM, Hodgkin PD, Nutt SL: Plasma cell ontogeny defined by quantitative changes in blimp-1 expression. J Exp Med. 2004, 200: 967-977. 10.1084/jem.20040973.PubMedCentralPubMed
101.
Delogu A, Schebesta A, Sun Q, Aschenbrenner K, Perlot T, Busslinger M: Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells. Immunity. 2006, 24: 269-281. 10.1016/j.immuni.2006.01.012.PubMed
102.
Nera KP, Kohonen P, Narvi E, Peippo A, Mustonen L, Terho P, Koskela K, Buerstedde JM, Lassila O: Loss of Pax5 promotes plasma cell differentiation. Immunity. 2006, 24: 283-293. 10.1016/j.immuni.2006.02.003.PubMed
103.
Medina F, Segundo C, Campos-Caro A, Salcedo I, Garcia-Poley A, Brieva JA: Isolation, maturational level, and functional capacity of human colon lamina propria plasma cells. Gut. 2003, 52: 383-389. 10.1136/gut.52.3.383.PubMedCentralPubMed
104.
Di Niro R, Mesin L, Raki M, Zheng NY, Lund-Johansen F, Lundin KE, Charpilienne A, Poncet D, Wilson PC, Sollid LM: Rapid generation of rotavirus-specific human monoclonal antibodies from small-intestinal mucosa. J Immunol. 2010, 185: 5377-5383. 10.4049/jimmunol.1001587.PubMed
105.
Terstappen LW, Johnsen S, Segers-Nolten IM, Loken MR: Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Blood. 1990, 76: 1739-1747.PubMed
106.
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.PubMed
107.
Arce E, Jackson DG, Gill MA, Bennett LB, Banchereau J, Pascual V: Increased frequency of pre-germinal center B cells and plasma cell precursors in the blood of children with systemic lupus erythematosus. J Immunol. 2001, 167: 2361-2369.PubMed
108.
Hoyer BF, Mumtaz IM, Loddenkemper K, Bruns A, Sengler C, Hermann K G, Maza S, Keitzer R, Burmester GR, Buttgereit F, Radbruch A, Hiepe F: Takayasu-arteritis is characterised by disturbances of B cell homeostasis and responds to B cell depletion therapy with rituximab. Ann Rheum Dis. 2012, 71: 75-79. 10.1136/ard.2011.153007.PubMed
109.
Hansen A, Odendahl M, Reiter K, Jacobi AM, Feist E, Scholze J, Burmester GR, Lipsky PE, Dorner T: Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjogren's syndrome. Arthritis Rheum. 2002, 46: 2160-2171. 10.1002/art.10445.PubMed
110.
Martinez-Gamboa L, Mei H, Loddenkemper C, Ballmer B, Hansen A, Lipsky PE, Emmerich F, Radbruch A, Salama A, Dorner T: Role of the spleen in peripheral memory B-cell homeostasis in patients with autoimmune thrombocytopenia purpura. Clin Immunol. 2009, 130: 199-212. 10.1016/j.clim.2008.09.009.PubMed
111.
Dass S, Rawstron AC, Vital EM, Henshaw K, McGonagle D, Emery P: Highly sensitive B cell analysis predicts response to rituximab therapy in rheumatoid arthritis. Arthritis Rheum. 2008, 58: 2993-2999. 10.1002/art.23902.PubMed
112.
Vital EM, Dass S, Buch MH, Henshaw K, Pease CT, Martin MF, Ponchel F, Rawstron AC, Emery P: B cell biomarkers of rituximab responses in systemic lupus erythematosus. Arthritis Rheum. 2011, 63: 3038-3047. 10.1002/art.30466.PubMed
113.
Kneitz C, Wilhelm M, Tony HP: Effective B cell depletion with rituximab in the treatment of autoimmune diseases. Immunobiology. 2002, 206: 519-527. 10.1078/0171-2985-00200.PubMed
114.
Pers JO, Devauchelle V, Daridon C, Bendaoud B, Le Berre R, Bordron A, Hutin P, Renaudineau Y, Dueymes M, Loisel S, Berthou C, Saraux A, Youinou P: BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjogren's syndrome. Arthritis Rheum. 2007, 56: 1464-1477. 10.1002/art.22603.PubMed
115.
Hekman A, Honselaar A, Vuist WM, Sein JJ, Rodenhuis S, ten Bokkel Huinink WW, Somers R, Rumke P, Melief CJ: Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody. Cancer Immunol Immunother CII. 1991, 32: 364-372. 10.1007/BF01741331.PubMed
116.
Vlasveld LT, Hekman A, Vyth-Dreese FA, Melief CJ, Sein JJ, Voordouw AC, Dellemijn TA, Rankin EM: Treatment of low-grade non-Hodgkin's lymphoma with continuous infusion of low-dose recombinant interleukin-2 in combination with the B-cell-specific monoclonal antibody CLB-CD19. Cancer Immunol Immunother CII. 1995, 40: 37-47.PubMed
117.
Gerber HP, Kung-Sutherland M, Stone I, Morris-Tilden C, Miyamoto J , McCormick R, Alley SC, Okeley N, Hayes B, Hernandez-Ilizaliturri FJ, McDonagh CF, Carter PJ, Benjamin D, Grewal IS: Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas. Blood. 2009, 113: 4352-4361. 10.1182/blood-2008-09-179143.PubMed
118.
Flavell DJ, Flavell SU, Boehm DA, Emery L, Noss A, Ling NR, Richardson PR, Hardie D, Wright DH: Preclinical studies with the anti-CD19-saporin immunotoxin BU12-SAPORIN for the treatment of human-B-cell tumours. Br J Cancer. 1995, 72: 1373-1379. 10.1038/bjc.1995.517.PubMedCentralPubMed
119.
Grossbard ML, Multani PS, Freedman AS, O'Day S, Gribben JG, Rhuda C, Neuberg D, Nadler LM: A phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin's lymphoma. Clin Cancer Res. 1999, 5: 2392-2398.PubMed
120.
Yazawa N, Hamaguchi Y, Poe JC, Tedder TF: Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease. Proc Natl Acad Sci USA. 2005, 102: 15178-15183. 10.1073/pnas.0505539102.PubMedCentralPubMed
121.
Sato S, Ono N, Steeber DA, Pisetsky DS, Tedder TF: CD19 regulates B lymphocyte signaling thresholds critical for the development of B-1 lineage cells and autoimmunity. J Immunol. 1996, 157: 4371-4378.PubMed
122.
Tedder TF, Inaoki M, Sato S: The CD19-CD21 complex regulates signal transduction thresholds governing humoral immunity and autoimmunity. Immunity. 1997, 6: 107-118. 10.1016/S1074-7613(00)80418-5.PubMed
123.
Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, Noppeney R, Viardot A, Hess G, Schuler M, Einsele H, Brandl C, Wolf A, Kirchinger P, Klappers P, Schmidt M, Riethmuller G, Reinhardt C, Baeuerle PA, Kufer P: Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008, 321: 974-977. 10.1126/science.1158545.PubMed
124.
Zalevsky J, Leung IW, Karki S, Chu SY, Zhukovsky EA, Desjarlais JR , Carmichael DF, Lawrence CE: The impact of Fc engineering on an anti-CD19 antibody: increased Fcγ receptor affinity enhances B-cell clearing in nonhuman primates. Blood. 2009, 113: 3735-3743. 10.1182/blood-2008-10-182048.PubMed
125.
Cardarelli PM, Rao-Naik C, Chen S, Huang H, Pham A, Moldovan-Loomis MC, Pan C, Preston B, Passmore D, Liu J, Kuhne MR, Witte A, Blanset D, King DJ: A nonfucosylated human antibody to CD19 with potent B-cell depletive activity for therapy of B-cell malignancies. Cancer Immunol Immunother CII. 2010, 59: 257-265. 10.1007/s00262-009-0746-z.PubMed
126.
Liu XY, Pop LM, Tsai L, Pop IV, Vitetta ES: Chimeric, divalent and tetravalent anti-CD19 monoclonal antibodies with potent in vitro and in vivo antitumor activity against human B-cell lymphoma and pre-B acute lymphoblastic leukemia cell lines. Int J Cancer. 2011, 129: 497-506. 10.1002/ijc.25695.PubMed
127.
Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M , Feldman SA, Maric I, Raffeld M, Nathan DA, Lanier BJ, Morgan RA, Rosenberg SA: Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010, 116: 4099-4102. 10.1182/blood-2010-04-281931.PubMedCentralPubMed
128.
Kochenderfer JN, Feldman SA, Zhao Y, Xu H, Black MA, Morgan RA, Wilson WH, Rosenberg SA: Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J Immunother. 2009, 32: 689-702. 10.1097/CJI.0b013e3181ac6138.PubMedCentralPubMed
129.
Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM, Yang JC, Kammula US, Devillier L, Carpenter R, Nathan DA, Morgan RA, Laurencot C, Rosenberg SA: B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012, 119: 2709-2720. 10.1182/blood-2011-10-384388.PubMedCentralPubMed
130.
Porter DL, Levine BL, Kalos M, Bagg A, June CH: Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011, 365: 725-733. 10.1056/NEJMoa1103849.PubMedCentralPubMed
131.
Savoldo B, Ramos CA, Liu E, Mims MP, Keating MJ, Carrum G, Kamble RT , Bollard CM, Gee AP, Mei Z, Liu H, Grilley B, Rooney CM, Heslop HE, Brenner MK, Dotti G: CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011, 121: 1822-1826. 10.1172/JCI46110.PubMedCentralPubMed
132.
Ochtrop ML, Goldacker S, May AM, Rizzi M, Draeger R, Hauschke D, Stehfest C, Warnatz K, Goebel H, Technau-Ihling K, Werner M, Salzer U, Eibel H, Schlesier M, Peter HH: T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency. Blood. 2011, 118: 309-318. 10.1182/blood-2010-11-321695.PubMed
133.
Goldacker S, Draeger R, Warnatz K, Huzly D, Salzer U, Thiel J, Eibel H, Schlesier M, Peter HH: Active vaccination in patients with common variable immunodeficiency (CVID). Clin Immunol. 2007, 124: 294-303. 10.1016/j.clim.2007.04.011.PubMed
134.
van der Kolk LE, Baars JW, Prins MH, van Oers MH: Rituximab treatment results in impaired secondary humoral immune responsiveness. Blood. 2002, 100: 2257-2259.PubMed
135.
van Assen S, Holvast A, Benne CA, Posthumus MD, van Leeuwen MA, Voskuyl AE, Blom M, Risselada AP, de Haan A, Westra J, Kallenberg CG, Bijl M: Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum. 2010, 62: 75-81. 10.1002/art.25033.PubMed
136.
Gelinck LB, Teng YK, Rimmelzwaan GF, van den Bemt BJ, Kroon FP, van Laar JM: Poor serological responses upon influenza vaccination in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. 2007, 66: 1402-1403. 10.1136/ard.2007.071878.PubMedCentralPubMed
137.
Bingham CO, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, Trzaskoma B, Martin F, Agarwal S, Kelman A: Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010, 62: 64-74. 10.1002/art.25034.PubMed
138.
Rehnberg M, Brisslert M, Amu S, Zendjanchi K, Hawi G, Bokarewa MI: Vaccination response to protein and carbohydrate antigens in patients with rheumatoid arthritis after rituximab treatment. Arthritis Res Ther. 2010, 12: R111-10.1186/ar3047.PubMedCentralPubMed
139.
Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T: Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004, 350: 2572-2581. 10.1056/NEJMoa032534.PubMed
140.
Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC: Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, doubleblind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006, 54: 2793-2806. 10.1002/art.22025.PubMed
141.
Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, Laubach J, Bawn SD, Gordon LI, Winter JN, Furman RR, Vose JM, Zelenetz AD, Mamtani R, Raisch DW, Dorshimer GW, Rosen ST, Muro K, Gottardi-Littell NR, Talley RL, Sartor O, Green D, Major EO, Bennett CL: Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood. 2009, 113: 4834-4840. 10.1182/blood-2008-10-186999.PubMedCentralPubMed
142.
Carter RH, Fearon DT: CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science. 1992, 256: 105-107. 10.1126/science.1373518.PubMed
143.
Dass S, Vital EM, Emery P: Development of psoriasis after B cell depletion with rituximab. Arthritis Rheum. 2007, 56: 2715-2718. 10.1002/art.22811.PubMed
144.
Mielke F, Schneider-Obermeyer J, Dorner T: Onset of psoriasis with psoriatic arthropathy during rituximab treatment of non-Hodgkin lymphoma. Ann Rheum Dis. 2008, 67: 1056-1057.PubMed
145.
Goetz M, Atreya R, Ghalibafian M, Galle PR, Neurath MF: Exacerbation of ulcerative colitis after rituximab salvage therapy. Inflamm Bowel Dis. 2007, 13: 1365-1368. 10.1002/ibd.20215.PubMed
146.
Benedetti L, Franciotta D, Vigo T, Grandis M, Fiorina E, Ghiglione E , Roccatagliata L, Mancardi GL, Uccelli A, Schenone A: Relapses after treatment with rituximab in a patient with multiple sclerosis and anti myelin-associated glycoprotein polyneuropathy. Arch Neurol. 2007, 64: 1531-1533. 10.1001/archneur.64.10.1531.PubMed
147.
Fillatreau S, Gray D, Anderton SM: Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol. 2008, 8: 391-397. 10.1038/nri2315.PubMed
148.
Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, Mauri C: CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity. 2010, 32: 129-140. 10.1016/j.immuni.2009.11.009.PubMed
149.
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: Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood. 2011, 117: 530-541. 10.1182/blood-2010-07-294249.PubMedCentralPubMed
150.
Lorenzi AR, Clarke AM, Wooldridge T, Waldmann H, Hale G, Symmons D, Hazleman BL, Isaacs JD: Morbidity and mortality in rheumatoid arthritis patients with prolonged therapy-induced lymphopenia: twelve-year outcomes. Arthritis Rheum. 2008, 58: 370-375. 10.1002/art.23122.PubMed
151.
Isaacs JD, Manna VK, Rapson N, Bulpitt KJ, Hazleman BL, Matteson EL, St Clair EW, Schnitzer TJ, Johnston JM: CAMPATH-1H in rheumatoid arthritis--an intravenous dose-ranging study. Br J Rheumatol. 1996, 35: 231-240. 10.1093/rheumatology/35.3.231.PubMed
152.
Isaacs JD, Greer S, Sharma S, Symmons D, Smith M, Johnston J, Waldmann H, Hale G, Hazleman BL: Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy-induced lymphopenia. Arthritis Rheum. 2001, 44: 1998-2008. 10.1002/1529-0131(200109)44:9<1998::AID-ART348>3.0.CO;2-T.PubMed
Metadata
Title
Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity
Authors
Henrik E Mei
Stefanie Schmidt
Thomas Dörner
Publication date
01-11-2012
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue Special Issue 5/2012
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3909
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