EN PL
REVIEW PAPER
Antibodies to citrullinated proteins – a new research directions
 
More details
Hide details
 
Online publication date: 2010-09-21
 
 
Reumatologia 2010;48(4):262-270
 
KEYWORDS
ABSTRACT
Rheumatoid arthritis is the most common, chronic inflammatory joint disease, which etiology still remains unknown. The diagnosis of this disease, despite the set diagnostic criteria, is still problematic, especially in the early stage. Promising laboratory parameter, which beside high specificity and peculiarity, has also huge prognostic value, are antibodies against citrullinated proteins ACPA. They can occur many years before the first symptoms of the disease onset, moreover are related with the presence of a shared epitope – SE, which predisposes to development of rheumatoid arthritis. The appearance of anticitullin antibodies results from excessive expression of citrullinated proteins in inflammatory tissues. Therefore, the identification of deiminated antigens, their localization and examination of functional changes induced by citrulination recently became an object of intensive research. High homology between human citrullinated α-enolase, which induces the production of antibodies, and bacterial enolase has drawn attention to the infectious aspect of the RA etiology. Porphyromonas gingivalis deserves special interest, the only microbe, which produces peptidylarginin deiminase – the enzyme responsible for citrulination in eucariot. The data shown in reviewed studies allow us better understanding of changes in the course of the disease and promise earlier diagnosis and implementation of treatment in the future.
 
REFERENCES (62)
1.
Nienhuis RL, Mandema E. A new serum factor in patients with rheumatoid arthritis; the antiperinuclear factor. Ann Rheum Dis 1964; 23: 302-305.  .
 
2.
Young BJ, Mallya RK, Leslie RD, et al. Anti-keratin antibodies in rheumatoid arthritis. Br Med J 1979; 2: 97-99.  .
 
3.
Simon M, Girbal E, Sebbag M, et al. The cytokeratin filament-aggregating protein filaggrin is the target of the so-called “antikeratin antibodies,” autoantibodies specific for rheumatoid arthritis. J Clin Invest 1993; 92: 1387-1393.  .
 
4.
Vossenaar ER, Després N, Lapointe E, et al. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res Ther 2004; 6: R142-150.  .
 
5.
Lundberg K, Kinloch A, Fisher BA. Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum 2008; 58: 3009-3019.  .
 
6.
Kinloch A, Lundberg K, Wait R, et al. Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis. Arthritis Rheum 2008; 58: 2287-2295.  .
 
7.
Nielen MM, van Schaardenburg D, Reesink HW, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 2004; 50: 380-386.  .
 
8.
Vossenaar ER, Zandman AJ, Van Venrooij WJ. Citrullination, a possible functional link between susceptibility genes and rheumatoid arthritis. Arthritis Res Ther 2004; 6: 1-5.  .
 
9.
Chang X, Yamada R, Suzuki A, et al. Citrullination of fibronectin in rheumatoid arthritis synovial tissue. Rheumatology (Oxford) 2005; 44: 1374-1382. .
 
10.
Chang X, Yamada R, Sawada T, et al. The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 2005; 44: 293-298. .
 
11.
Takizawa T, Suzuki A, Sawada T, et al. Citrullinated fibrinogen detected as a soluble citrullinated autoantigen in rheumatoid arthritis synovial fluids. Ann Rheum Dis 2006; 65: 1013-1020. .
 
12.
Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987; 30: 1205-1213. .
 
13.
Reviron D, Perdriger A, Toussirot E, et al. Influence of shared epitope-negative HLA-DRB1 alleles on genetic susceptibility to rheumatoid arthritis. Arthritis Rheum 2001; 44: 535-540. .
 
14.
Hammer J, Bono E, Gallazzi F, et al. Precise prediction of major histocompatibility complex class II-peptide interaction based on peptide side chain scanning. J Exp Med 1994; 180: 2353-2358. .
 
15.
Hill JA, Southwood S, Sette A, et al. 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 2003; 171: 538-541. .
 
16.
Weyand CM, McCarthy TG, Goronzy JJ. Correlation between disease phenotype and genetic heterogeneity in rheumatoid arthritis. J Clin Invest 1995; 95: 2120-2126. .
 
17.
Kowalski MK, Hilt J, Strańczyk J i wsp. Związek polimorfizmu genów HLA-DRB1 z występowaniem i wykładnikami ciężkości przebiegu reumatoidalnego zapalenia stawów. Alergia Astma Immunologia 2001; 6: 51-56. .
 
18.
Ioan-Facsinay A, Willemze A, Robinson DB, et al. Marked differences in fine specificity and isotype usage of the anti-citrullinated protein antibody in health and disease. Arthritis Rheum 2008; 58: 3000-3008. .
 
19.
El-Gabalawy HS, Robinson DB, Hart D, et al. Immunogenetic risks of anti-cyclical citrullinated peptide antibodies in a North American Native population with rheumatoid arthritis and their first-degree relatives. J Rheumatol 2009; 36: 1130-1135. .
 
20.
Linn-Rasker SP, van der Helm-van Mil AH, van Gaalen FA, et al. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis 2006; 65: 366-371. .
 
21.
Huizinga TW, Amos CL, van der Helm-van Mil AH, et al. Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum 2005; 52: 3433-3438. .
 
22.
Klareskog L, Stolt P, Lundberg K, et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 2006; 54: 38-46. .
 
23.
Källberg H, Jacobson S, Bengtsson C, et al. Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case-control studies. Ann Rheum Dis 2009; 68: 222-227. .
 
24.
Chang X, Yamada R, Suzuki A, et al. Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis. Rheumatology (Oxford) 2005; 44: 40-50. .
 
25.
Suzuki A, Yamada R, Chang X, et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 2003; 34: 395-402. .
 
26.
Vossenaar ER, Radstake TR, van der Heijden A, et al. Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Ann Rheum Dis 2004; 63: 373-381. .
 
27.
Masson-Bessi?re C, Sebbag M, Girbal-Neuhauser E, 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 2001; 166: 4177-4184. .
 
28.
Cutolo M, Sulli A, Barone A, et al. Macrophages, synovial tissue and rheumatoid arthritis. Clin Exp Rheumatol 1993; 11: 331-339. .
 
29.
Rodenburg RJ, Ganga A, van Lent PL, et al. The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis. Arthritis Rheum 2000; 43: 1941-1950. .
 
30.
Chapuy-Regaud S, Sebbag M, Baeten D, et al. Fibrin deimination in synovial tissue is not specific for rheumatoid arthritis but commonly occurs during synovitides. J Immunol 2005; 174: 5057-5064. .
 
31.
Senshu T, Kan S, Ogawa H, et al. Preferential deimination of keratin k1 and filaggrin during the terminal differentiation of human epidermis. Biochem Biophys Res Commun 1996; 225: 712-719. .
 
32.
Osung OA, Chandra M, Holborov EJ. Intermediate filaments in synovial lining cells in rheumatoid arthritis and other arthritides are of vimentin type. Ann Rheum Dis 1982; 41: 74-77. .
 
33.
Martys JL, Ho CL, Liem RK, Gundersen GG. Intermediate filaments in motion: observations of intermediate filaments in cells using green fluorescent protein-vimentin. Mol Biol Cell 1999; 10: 1289-1295. .
 
34.
Mor-Vaknin N, Punturieri A, Sitwala K, Markovitz DM. Vimentin is secreted by activated macrophages. Nat Cell Biol 2003; 5: 59-63. .
 
35.
Moisan E, Girard D. Cell surface expression of intermediate filament proteins vimentin and lamin B1 in human neutrophil spontaneous apoptosis. J Leukoc Biol 2006; 79: 489-498. .
 
36.
Tilleman K, Van Steendam K, Cantaert T, et al. Synovial detection and autoantibody reactivity of processed citrullinated isoforms of vimentin in inflammatory arthritides. Rheumatology (Oxford) 2008; 47: 597-604. .
 
37.
Byun Y, Chen F, Chang R, et al. Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis. Cell Death Differ 2001; 8: 443-450. .
 
38.
Yasuda T, Kakinuma T, Julovi SM, et al. COOH-terminal heparin-binding fibronectin fragment induces nitric oxide production in rheumatoid cartilage through CD44. Rheumatology (Oxford) 2004; 43: 1116-1120. .
 
39.
Yasuda T, Poole AR. A fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1-mediated pathway. Arthritis Rheum 2002; 46: 138-148. .
 
40.
Clavel G, Bessis N, Boissier MC. Recent data on the role of angiogenesis in rheumatoid arthritis. Joint Bone Spine 2003; 70: 321-326. .
 
41.
Lee SS, Joo YS, Kim WU, et al. Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol 2001; 19: 321-324. .
 
42.
Wijelath ES, Murray J, Rahman S, et al. Novel vascular endothelial growth factor binding domains of fibronectin enhance vascular endothelial growth factor biological activity. Circ Res 2002; 91: 25-31. .
 
43.
Maragoudakis ME, Kraniti N, Giannopoulou E, et al. Modulation of angiogenesis and progelatinase a by thrombin receptor mimetics and antagonists. Endothelium 2001; 8: 195-205. .
 
44.
Esmon CT. Role of coagulation inhibitors in inflammation. Thromb Haemost 2001; 86: 51-56. .
 
45.
Zhao X, Okeke NL, Sharpe O, et al. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis. Arthritis Res Ther 2008; 10: R94. .
 
46.
Wright SD, Weitz JI, Huang AJ, et al. Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. Proc Natl Acad Sci U S A 1988; 85: 7734-7738. .
 
47.
Ishikawa H, Hirata S, Andoh Y, et al. An immunohistochemical and immunoelectron microscopic study of adhesion molecules in synovial pannus formation in rheumatoid arthritis. Rheumatol Int 1996; 16: 53-60. .
 
48.
Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol 2001; 167: 2887-2894. .
 
49.
Clavel C, Nogueira L, Laurent L, et al. Induction of macrophage secretion of tumor necrosis factor alpha through Fcgamma receptor IIa engagement by rheumatoid arthritis-specific autoantibodies to citrullinated proteins complexed with fibrinogen. Arthritis Rheum 2008; 58: 678-688. .
 
50.
Nakayama-Hamada M, Suzuki A, Furukawa H, et al. Citrullinated fibrinogen inhibits thrombin-catalysed fibrin polymerization. J Biochem 2008; 144: 393-398. .
 
51.
Busso N, Péclat V, Van Ness K, et al. Exacerbation of antigen-induced arthritis in urokinase-deficient mice. J Clin Invest 1998; 102: 41-50. .
 
52.
Seweryn E, Pietkiewicz J, Szamborska A i wsp. Enolaza na powierzchni komórek eukariota i prokariota jako receptor plazminogenu ludzkiego. Postępy Hig Med Dośw 2007; 61: 672-682. .
 
53.
Snyderman R, McCarty GA. Analogous mechanisms of tissue destruction in rheumatoid arthritis and periodontal disease. In: Host-Parasite Interaction in Perodontal Diseases. Genco RJ, Mergenhagen SE (eds). American Society of Microbiology, Washington 1982; 354-362. .
 
54.
Gleissner C, Willershausen B, Kaesser U, Bolten WW. The role of risk factor for periodontal disease in patients with rheumatoid arthritis. Eur J Med Res 1998; 3: 387-392. .
 
55.
Kässer UR, Gleissner C, Dehne F, et al. Risk for periodontal disease in patients with longstanding rheumatoid arthritis. Arthritis Rheum 1997; 40: 2248-2251. .
 
56.
Rosenstein ED, Greenwald RA, Kushner LJ, Weissmann G. Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation 2004; 28: 311-318. .
 
57.
Moen K, Brun JG, Valen M, et al. Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs. Clin Exp Rheumatol 2006; 24: 656-663. .
 
58.
De Pablo p, Chapple ILC, Buckley CD, et al. Periodontosis in systemic rheumatic diseases. Nat Rev Rheumatol 2009; 5: 218-224. .
 
59.
Loos BG, John RP, Laine ML. Identification of genetic risk factors for periodontitis and possible mechanisms of action. J Clin Periodontol 2005; 32 Suppl 6: 159-179. .
 
60.
Słotwińska SM. Mikrobiologia zapaleń przyzębia na podstawie piśmiennictwa i badań własnych. Część II: Porphyromonas gingivalis, Prevotella intrmedia. Nowa stomatologia 2005; 3: 151-154. .
 
61.
McGraw WT, Potempa J, Farley D, Travis J. Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infect Immun 1999; 67: 3248-3256. .
 
62.
Klareskog L, Rönnelid J, Lundberg K, et al. Immunity to citrullinated proteins in rheumatoid arthritis. Annu Rev Immunol 2008; 26: 651-675.
 
Copyright: © Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (https://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
eISSN:2084-9834
ISSN:0034-6233
Journals System - logo
Scroll to top