Article information
Hasta hace poco tiempo se consideraba que las células B tenían un papel secundario en la patogenia de la artritis reumatoide, limitado a la producción de autoanticuerpos. Sin embargo, la sorprendente buena respuesta clínica que la depleción sistémica de las células B ha demostrado en ensayos clínicos controlados y aleatorizados con pacientes con artritis reumatoide ha revitalizado el interés por el papel del linfocito B en la patogenia de esta enfermedad autoinmunitaria. Diversas evidencias indican que las células B pueden regular el curso de la respuesta inmunitaria mediante mecanismos alternativos no dependientes de la producción de anticuerpos. Estos mecanismos incluyen la presentación de antígenos y la liberación de factores solubles como citocinas proinflamatorias, metaloproteasas y quimiocinas. En esta revisión se resumen los datos experimentales que indican que la célula B participa en la patogenia de la arthritis reumatoide mediante un mecanismo multifactorial.
Palabras clave:
Linfocito B
Artritis reumatoide
Patogenia
Classically, B-cells have been considered to play a secondary role in the pathogenesis of rheumatoid artritis, restricted to the production of auto-antibodies. Nevertheless, the unexpected good clinical response that the systemic depletion of B-cells has demonstrated in a well-controlled clinical trial in patients with rheumatoid artritis has revitalized the interest in this cell type in the pathogenesis of this autoimmune disease. Several evidences suggest that B-cells can regulate the course of the immune response through antibody productionindependent mechanisms. These mechanisms include antigen presentation and the release of soluble factors such as proinflammatory cytokines, metalloproteinases, and chemokines. This article reviews experimental data supporting that the participation of B-cells in the pathogenesis of rheumatoid arthritis occurs through multiple mechanisms.
Keywords:
B-Lymphocites
Rheumatoid arthritis
Pathogenesis
Full text is only aviable in PDF
Bibliografía
[2.]
C. Turesson, L. Jacobsson, U. Bergstrom.
Extra-articular rheumatoid arthritis: prevalence and mortality.
Rheumatology (Oxford), 38 (1999), pp. 668-674
[3.]
J.B. Smith, M.K. Haynes.
Rheumatoid arthritis –a molecular understanding.
Ann Intern Med, 136 (2002), pp. 908-922
[4.]
B.L. Kotzin, J. Kappler.
Targeting the T cell receptor in rheumatoid arthritis.
Arthritis Rheum, 41 (1998), pp. 1906-1910
[5.]
L.S. Davis, H. Schulze-Koops, P.E. Lipsky.
Human CD4+ T cell differentiation and effector function: implications for autoimmunity.
Immunol Res, 19 (1999), pp. 25-34
[6.]
G.S. Firestein, N.J. Zvaifler.
How important are T cells in chronic rheumatoid synovitis?.
Arthritis Rheum, 33 (1990), pp. 768-773
[7.]
J.C. Edwards, L. Szczepanski, J. Szechinski, A. Filipowicz-Sosnowska, P. Emery, D.R. Close, et al.
Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.
N Engl J Med, 350 (2004), pp. 2572-2581
[8.]
A.E. Schroder, A. Greiner, C. Seyfert, C. Berek.
Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis.
Proc Natl Acad Sci U S A, 93 (1996), pp. 221-225
[9.]
Y. Yamanishi, G.S. Firestein.
Pathogenesis of rheumatoid arthritis: the role of synoviocytes.
Rheum Dis Clin North Am, 27 (2001), pp. 355-371
[10.]
G.S. Firestein.
Evolving concepts of rheumatoid arthritis.
Nature, 423 (2003), pp. 356-361
[11.]
T.V.J. Gallart, M. Lopez-Botel.
Organos y células del sistema inmunitario.
Medicina Interna, Harcourt, (2000),
[12.]
J.C. Edwards, G. Cambridge.
B-cell targeting in rheumatoid arthritis and other autoimmune diseases.
Nat Rev Immunol, 6 (2006), pp. 394-403
[13.]
B.G.C. Diamond.
B cells.
Kelley’s Textbook of Rheumatology, 7.a ed., pp. 153-174
[14.]
C.M. Weyand, J.J. Goronzy, S. Takemura, P.J. Kurtin.
Cell-cell interactions in synovitis. Interactions between T cells and B cells in rheumatoid arthritis.
Arthritis Res, 2 (2000), pp. 457-463
[15.]
C.M. Weyand, T.M. Seyler, J.J. Goronzy.
B cells in rheumatoid synovitis.
Arthritis Res Ther, 7 (2005), pp. S9-S12
[16.]
S. Takemura, A. Braun, C. Crowson, P.J. Kurtin, R.H. Cofield, W.M. O’Fallon, et al.
Lymphoid neogenesis in rheumatoid synovitis.
J Immunol, 167 (2001), pp. 1072-1080
[17.]
S. Takemura, P.A. Klimiuk, A. Braun, J.J. Goronzy, C.M. Weyand.
T cell activation in rheumatoid synovium is B cell dependent.
J Immunol, 167 (2001), pp. 4710-4718
[18.]
J.C. Edwards, G. Cambridge.
Rheumatoid arthritis: the predictable effect of small immune complexes in which antibody is also antigen.
Br J Rheumatol, 37 (1998), pp. 126-130
[19.]
V. Pistoia, A. Corcione.
Relationships between B cell cytokine production in secondary lymphoid follicles and apoptosis of germinal center B lymphocytes.
Stem Cells, 13 (1995), pp. 487-500
[20.]
C. Trocme, P. Gaudin, S. Berthier, C. Barro, P. Zaoui, F. Morel.
Human B lymphocytes synthesize the 92-kDa gelatinase, matrix metalloproteinase- 9.
J Biol Chem, 273 (1998), pp. 20677-20684
[21.]
S.K. Pierce, J.F. Morris, M.J. Grusby, P. Kaumaya, A. Van Buskirk, M. Srinivasan, et al.
Antigen-presenting function of B lymphocytes.
Immunol Rev, 106 (1988), pp. 149-180
[22.]
N.J. Zvaifler.
The immunopathology of joint inflammation in rheumatoid arthritis.
Adv Immunol, 16 (1973), pp. 265-336
[23.]
J.H. Vaughan.
1992 Joseph J. Bunim Lecture. Pathogenetic concepts and origins of rheumatoid factor in rheumatoid arthritis.
Arthritis Rheum, 36 (1993), pp. 1-6
[24.]
D. Mewar, A.G. Wilson.
Autoantibodies in rheumatoid arthritis: a review.
Biomed Pharmacother, 60 (2006), pp. 648-655
[25.]
M. Wahle, M. Pierer, A. Krause, S. Kolker, C.G. Baerwald.
Decreased catecholamine- induced cell death in B lymphocytes from patients with rheumatoid arthritis.
Ann N Y Acad Sci, 966 (2002), pp. 425-428
[26.]
R. Goldbach-Mansky, J. Lee, A. McCoy, J. Hoxworth, C. Yarboro, J.S. Smolen, et al.
Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset.
Arthritis Res, 2 (2000), pp. 236-243
[27.]
D. Baeten, I. Peene, A. Union, L. Meheus, M. Sebbag, G. Serre, et al.
Specific presence of intracellular citrullinated proteins in rheumatoid arthritis synovium: relevance to antifilaggrin autoantibodies.
Arthritis Rheum, 44 (2001), pp. 2255-2262
[28.]
E.R. Vossenaar, T.J. Smeets, M.C. Kraan, J.M. Raats, W.J. Van Venrooij, P.P. Tak.
The presence of citrullinated proteins is not specific for rheumatoid synovial tissue.
Arthritis Rheum, 50 (2004), pp. 3485-3494
[29.]
K.A. Kuhn, L. Kulik, B. Tomooka, K.J. Braschler, W.P. Arend, W.H. Robinson, et al.
Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis.
J Clin Invest, 116 (2006), pp. 961-973
[30.]
G.A. Schellekens, H. Visser, B.A. De Jong, F.H. Van den Hoogen, J.M. Hazes, F.C. Breedveld, et al.
The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide.
Arthritis Rheum, 43 (2000), pp. 155-163
[31.]
M.A. Van Boekel, E.R. Vossenaar, F.H. Van den Hoogen, W.J. Van Venrooij.
Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value.
Arthritis Res, 4 (2002), pp. 87-93
[32.]
I. Matsumoto, A. Staub, C. Benoist, D. Mathis.
Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme.
Science, 286 (1999), pp. 1732-1735
[33.]
F.A. Van Gaalen, R.E. Toes, H.J. Ditzel, M. Schaller, F.C. Breedveld, C.L. Verweij, et al.
Association of autoantibodies to glucose-6-phosphate isomerase with extraarticular complications in rheumatoid arthritis.
Arthritis Rheum, 50 (2004), pp. 395-399
[34.]
C.A. Herve, R. Wait, P.J. Venables.
Glucose-6-phosphate isomerase is not a specific autoantigen in rheumatoid arthritis.
Rheumatology (Oxford), 42 (2003), pp. 986-988
[35.]
M. Schaller, W. Stohl, S.M. Tan, V.M. Benoit, D.M. Hilbert, H.J. Ditzel.
Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial fluid from patients with inflammatory arthritis.
Ann Rheum Dis, 64 (2005), pp. 743-749
[36.]
C.C. Chou, Y.J. Sun, M. Meng, C.D. Hsiao.
The crystal structure of hosphoglucoseisomerase/autocrine motility factor/neuroleukin complexed with its carbohydrate phosphate inhibitors suggests its substrate/receptor recognition.
J Biol Chem, 275 (2000), pp. 23154-23160
[37.]
Y.J. Sun, C.C. Chou, W.S. Chen, R.T. Wu, M. Meng, C.D. Hsiao.
The crystal structure of a multifunctional protein: phosphoglucose isomerase/autocrine motility factor/neuroleukin.
Proc Natl Acad Sci U S A, 96 (1999), pp. 5412-5417
[38.]
I. Matsumoto, M. Maccioni, D.M. Lee, M. Maurice, B. Simmons, M. Brenner, et al.
How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease.
Nat Immunol, 3 (2002), pp. 360-365
[39.]
V. Pistoia.
Production of cytokines by human B cells in health and disease.
Immunol Today, 18 (1997), pp. 343-350
[40.]
M.E. Duddy, A. Alter, A. Bar-Or.
Distinct profiles of human B cell effector cytokines: a role in immune regulation?.
J Immunol, 172 (2004), pp. 3422-3427
[41.]
J.M. Alvaro-Gracia, N.J. Zvaifler, G.S. Firestein.
Cytokines in chronic inflammatory arthritis. V. Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on HLA-DR expression, proliferation, collagenase production, and granulocyte macrophage colony-stimulating factor production by rheumatoid arthritis synoviocytes.
J Clin Invest, 86 (1990), pp. 1790-1798
[42.]
G.K. Kumkumian, R. Lafyatis, E.F. Remmers, J.P. Case, S.J. Kim, R.L. Wilder.
Platelet-derived growth factor and IL-1 interactions in rheumatoid arthritis. Regulation of synoviocyte proliferation, prostaglandin production, and collagenase transcription.
J Immunol, 143 (1989), pp. 833-837
[43.]
A. Braun, S. Takemura, A.N. Vallejo, J.J. Goronzy, C.M. Weyand.
Lymphotoxin beta-mediated stimulation of synoviocytes in rheumatoid arthritis.
Arthritis Rheum, 50 (2004), pp. 2140-2150
[44.]
R. Garcia-Vicuna, M.V. Gomez-Gaviro, M.J. Dominguez-Luis, M.K. Pec, I. Gonzalez-Alvaro, J.M. Alvaro-Gracia, et al.
CC and CXC chemokine receptors mediate migration, proliferation, and matrix metalloproteinase production by fibroblast-like synoviocytes from rheumatoid arthritis patients.
Arthritis Rheum, 50 (2004), pp. 3866-3877
Copyright © 2007. Elsevier España S.L Barcelona
