Article information
Abstract
Rheumatoid arthritis is an autoimmune disease of multifactorial etiology characterized by inflammation of the joints and presence of autoantibodies directed against multiple autoantigens. Recently the study of the anti-citrullinated protein antibodies (ACP) has acquired great interest due to its high specificity and sensitivity for diagnosis, in addition to which it has shown to be a predictor of severity in patients with rheumatoid arthritis, suggesting an important participation in the pathogenesis of the disease.
Keywords:
Citrullination
Rheumatoid arthritis
Anti-citrullinated protein antibodies
Resumen
La artritis reumatoide es una enfermedad autoinmune de etiología multifactorial caracterizada por inflamación de las articulaciones y presencia de múltiples autoanticuerpos. Recientemente, el estudio de los anticuerpos antiproteínas citrulinadas (APS) ha adquirido gran interés debido a su alta especificidad y sensibilidad para el diagnóstico, además de que se ha demostrado que es predictor de severidad en pacientes con artritis reumatoide; lo cual sugiere un papel importante en la patogénesis de la enfermedad.
Palabras clave:
Citrulinación
Artritis reumatoide
Anticuerpos antiproteínas citrulinadas
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References
[1.]
M.C. Hochberg, T.D. Spector.
Epidemiology of rheumatoid arthritis: update.
Epidem Rev., 12 (1990), pp. 247-252
[2.]
Pascual GE. Manifestaciones clínicas articulares. In: Arán, editor. Tratado de Reumatología. España. 1998; p. 437-8.
[3.]
P.K. Gregersen, J. Silver, R.J. Winchester.
The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis.
Arthritis & Rheum., 30 (1987), pp. 1205-1213
[4.]
F.C. Arrnett, S.M. Edworthy, D.A. Bloch, D.J. McShane, J.F. Fries, N.S. Cooper, et al.
The American Rheumatism Association 1987 revised criteria for classification of Rheumatoid Arthritis.
Arthitis & Rheum., 31 (1988), pp. 315-324
[5.]
D. Nemazee.
Immune complex can trigger specific, T-cell dependent, autoanti-IgG antibody production in mice.
J Exp Med., 161 (1985), pp. 242-256
[6.]
F.A. Van Gaalen, S.P. Linn-Rasker, W.J. Van Venrooij, B.A. De Jong, F.C. Breedveld, C.L. Verweij, et al.
Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study.
Arthritis & Rheum., 50 (2004), pp. 709-715
[7.]
C.H. Van Jaarsveld, E.J. Ter Borg, J.W. Jacobs, G.A. Schellekens, F.H. Gmelig-Meylinq, C. Van Booma-Frankfort, et al.
The prognostic value of the antiperinuclear factor, anticitrullinated peptide autoantibodies and rheumatoid factor in early rheumatoid arthritis.
Clin Exp Rheumatol., 17 (1999), pp. 689-697
[8.]
X. Zeng, M. Ai, X. Tian, X. Gan, Y. Shi, Q. Song.
Diagnostic value of anti-cyclic citrullinated peptide antibody in patients with rheumatoid Arthritis.
J Rheumatol., 30 (2003), pp. 1451-1455
[9.]
M. Sebbag, M. Simon, C. Vincent, C. Masson-Bessière, E. Girbal, J.J. Durieux, et al.
The antiperinucleal factor and the so called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies.
J Clin Invest., 95 (1995), pp. 2672-2679
[10.]
E.R. Vossenaar, N. Després, E. Lapointe, A. Van der Heijden, M. Lora, T. Senshu, et al.
Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin.
Arthritis Res Ther., 6 (2004), pp. 142-150
[11.]
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
[12.]
W.J. Van Venrooij, G.J. Pruijn.
Citrullination: a small change for a protein with great consequences for rheumatoid arthritis.
Arthritis Res., 2 (2000), pp. 249-251
[13.]
E. Tarcsa, L.N. Marekov, G. Mei, G. Melino, S.C. Lee, P.M. Steinert.
Protein unfolding by peptidylarginine deiminase. Substrate specificity and structural relation ships of the natural substrate strichohyalin and filaggrin.
J Biol Chem., 271 (1996), pp. 30709-30716
[14.]
M.M. Nielen, D. Van Schaardenburg, H.W. Reesink, R.J. Van de Stadt, I.E. Van der Horst- Bruinsma, M.H. De Koning, et al.
Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors.
Arthritis & Rheum., 50 (2004), pp. 380-386
[15.]
D.S. Majka, K.D. Deane, L.A. Parrish, A.A. Lazar, A.E. Barón, C.W. Walker, et al.
Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis.
Ann Rheum Dis., 67 (2008), pp. 801-807
[16.]
E.R. Vossenaar, A.J. Zendman, W.J. Van Venrooij, G.J. Prujin.
PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease.
Bioassays., 25 (2003), pp. 1106-1118
[17.]
X. Chang, R. Yamada, A. Suzuki, T. Sawada, S. Yoshino, S. Tokuhiro, et al.
Localization of peptidylarginine deiminase 4(PADI4) and citrullinated proteinin synovial tissue of rheumatoid arthritis.
Rheumatology., 44 (2005), pp. 40-50
[18.]
A. Kinloch, K. Lundberg, R. Wait, N. Wegner, N.H. Lim, A.J. Zendman, et al.
Synovial fluid is a site citrullination of autoantigens in inflammatory arthritis.
Arthritis & Rheum., 58 (2008), pp. 2287-2295
[19.]
A. Suzuki, R. Yamada, X. Chang, S. Tokuhiro, T. Sawada, M. Susuki, et al.
Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis.
Nat Genet., 34 (2003), pp. 395-402
[20.]
L. Caponi, E. Petit-Teixeira, M. Sebbag, F. Bongiorni, S. Moscato, F. Pratesi, et al.
A family based study shows no association between rheumatoid arthritis and the PADI4 gene in a white French population.
Ann Rheum Dis., 64 (2005), pp. 587-593
[21.]
A. Barton, J. Bowes, S. Eyre, K. Spreckley, A. Hinks, S. John, et al.
A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population.
Arthritis & Rheum., 50 (2004), pp. 1117-1121
[22.]
A. Martinez, A. Valdivia, D. Pascual-Salcedo, J.R. Lamas, M. Fernández-Arquero, A. Balsa, et al.
PADI4 polymorphisms are not associated with rheumatoid arthritis in the Spanish population.
Rheumatology., 44 (2005), pp. 1263-1266
[23.]
C.P. Kang, H.S. Lee, H. Ju, H. Cho, C. Kang, S.C. Bae.
A functional haplotype of the PADI4 gene associated with increased rheumatoid arthritis susceptibility in Koreans.
Arthritis & Rheum., 54 (2006), pp. 90-96
[24.]
R.L. Nijenhuis, E. Mandema.
A new serum factor in patients with rheumatoid arthritis; The antiperinuclear factor.
Ann Rheum Dis., 23 (1964), pp. 302-305
[25.]
B.J. Young, R.K. Mallya, R.D. Leslie, C.J. Clark, T.J. Hamblin.
Anti-keratin antibodies in rheumatoid arthritis.
Br Med J., 2 (1979), pp. 97-99
[26.]
M. Sebbag, M. Simon, C. Vincent, C. Masson-Bessière, E. Girbal, J.J. Durieux, et al.
The antiperinucleal factor and the so called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies.
J Clin Invest., 95 (1995), pp. 2672-2679
[27.]
E. Girbal-Neuhauser, J.J. Durieux, M. Arnaud, P. Dalbon, M. Sebag, C. Vincent, T. Senshu, et al.
The epitopes targeted by the rheumatoid arthritis-associated antifilagrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deamination of arginine residues.
J Immunol., 162 (1999), pp. 585-594
[28.]
C. Masson-Bessière, M. Sebbag, E. Girbal-Neuhauser, L. Nogueira, C. Vincent, et al.
The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the alpha-and beta-chains of fibrin.
J Immunol., 166 (2001), pp. 4177-4184
[29.]
A.D. Cook, R. Gray, J. Ramshaw, I. Mackay, M. Rowley.
Antibodies against the CB10 fragment of type II collagen in rheumatoid arthritis.
Arthritis Res Ther., 6 (2004), pp. R477-R483
[30.]
A. Suzuki, R. Yamada, M. Ohtake-Yamanaka, Y. Okazaki, T. Sawada, K. Yamamoto.
Anticitrullinated collagen type I antibody is a target of autoimmunity in rheumatoid arthritis.
Biochem Byophys Res Commun., 333 (2005), pp. 418-426
[31.]
K. Tilleman, K. Steendam, T. Cantaert, F. De Keyser, D. Elewaut, D. Deforce.
Synovial detection and autoantibody reactivity of processed citrullinate disoforms of vimentin in inflammatory arthritides.
Rheumatology., 47 (2008), pp. 597-604
[32.]
K. Matsuo, Y. Xiang, H. Nakamura, K. Masuko, K. Yudoh, K. Noyori, et al.
Identification of novel citrullinated autoantigens of synoviumin rheumatoid arthritis using a proteomic approach.
Arthritis Res Ther., 8 (2006), pp. R175
[33.]
A. Kinloch, V. Tatzer, R. Wait, D. Peston, K. Lundberg, P. Donatien, et al.
Identification of citrullinated alpha-enolase as a candidate autoantigen in rheumatoid arthritis.
Arthritis Res Ther., 7 (2005), pp. R1421-R1429
[34.]
E. Olivares-Martínez.
Identificación de los péptidos reconocidos por los anticuerpos anti-péptidos citrulinados presentes en los pacientes con artritis temprana.
Tesis de Maestría,
[35.]
K. Lundberg, S. Nijenhuis, E.R. Vossenaar, K. Palmblad, W.J. Van Venrooij, L. Klareskog, et al.
Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity.
Arthritis Res Ther., 7 (2005), pp. R458-R467
[36.]
J.A. Hill, S. Southwood, A. Sette, A.M. Jevnikar, D.A. Bell, E. Cairns.
Cutting Edge: The conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule.
J Immunol., 171 (2003), pp. 538-541
[37.]
J.A. Hill, D.A. Bell, W. Brintnell, D. Yue, B. Wehlrli, A.M. Jevnikar, et al.
Artrhritis induced by posttranslationally modified (citrullinated) fibrinogenin DR4-IE transgenic mice.
J Exp Med., 205 (2008), pp. 967-979
[38.]
L. Klareskog, P. Stolt, K. Lundberg, H. Källberg, C. Bengston, J. Grunewald, et al.
A new model for etiology of rheumatoid arthritis: smoking may tigger HLA-DR (shared epitope)-restricted immune reactions to antigens modified by citrullination.
Arhritis Rheum., 54 (2006), pp. 38-46
[39.]
D. Makrygiannakis, M. Hermansson, A.K. Ulfgren, A.P. Nicholas, A.J. Zendman, A. Eklund, et al.
Smoking increases peptidy larginin edeiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells.
Ann Rheum Dis., 10 (2008), pp. 826-850
[40.]
L. Klareskog, J. Rönnelid, K. Lundberg, L. Padyukov, L. Alfredsson.
Immuneto Citrullinated Proteins in rheumatoid arthritis.
Ann Rev Immunol., 26 (2008), pp. 651-675
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