Physiologic Target, Molecular Evolution, and Pathogenic Functions of a Monoclonal Anti-Citrullinated Protein Antibody Obtained From a Patient With Rheumatoid Arthritis.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
08
12
2019
accepted:
25
06
2020
pubmed:
6
7
2020
medline:
5
1
2021
entrez:
5
7
2020
Statut:
ppublish
Résumé
In plasma from a patient with rheumatoid arthritis (RA), we previously isolated a human monoclonal anti-citrullinated protein antibody (ACPA), CCP-Ab1, that recognizes various citrullinated antigens. In this study, we aimed to explore the physiologic target of CCP-Ab1 and the role of molecular evolution, through affinity maturation, of this ACPA in the onset and the exacerbation of RA. The target protein of CCP-Ab1 was identified in the plasma of a patient with RA and purified under native conditions. Germline-reverted (GL-rev) CCP-Ab1 was generated, and its reactivity was compared to that of mature CCP-Ab1. The functions of CCP-Ab1 and GL-rev CCP-Ab1 in the onset or exacerbation of autoimmune arthritis were analyzed using autoimmune arthritis-prone SKG mice. CCP-Ab1 bound citrullinated fibrinogen under native conditions. In cultures with GL-rev CCP-Ab1, the binding affinity to citrullinated fibrinogen was drastically reduced (P < 0.05). The elements implicated in GL-rev CCP-Ab1 binding to a citrullinated peptide, cfc1-cyc, were almost identical to those implicated in CCP-Ab1 binding. In arthritis-prone SKG mice, CCP-Ab1, but not GL-rev CCP-Ab1, induced significant exacerbation of experimental arthritis (P < 0.05). Increased production of interleukin-6, both in the joint tissue and in the serum, was observed in SKG mice treated with CCP-Ab1 compared to those treated with GL-rev CCP-Ab1 (P < 0.05). Furthermore, the immune complex formed by CCP-Ab1 and fibrinogen was detected at higher concentrations in the synovial tissue of SKG mice administered CCP-Ab1 (P < 0.05 versus control treatment groups). These data show that germline-encoded CCP-Ab1, which binds weakly to citrullinated fibrinogen, undergoes hypermutation through the activation of naive B cells by citrullinated peptides/proteins, thereby stimulating high reactivity to citrullinated fibrinogen. These findings deepen our understanding of the role of molecular evolution of ACPAs in the onset and exacerbation of RA.
Substances chimiques
Anti-Citrullinated Protein Antibodies
0
Autoantigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2040-2049Informations de copyright
© 2020, American College of Rheumatology.
Références
Carmona L, Cross M, Williams B, Lassere M, March L. Rheumatoid arthritis. Best Pract Res Clin Rheumatol 2010;24:733-45.
Van Venrooij WJ, van Beers JJ, Pruijn GJ. Anti-CCP antibody, a marker for the early detection of rheumatoid arthritis. Ann N Y Acad Sci 2008;1143:268-85.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81.
Van Venrooij WJ, van Beers JJ, Pruijn GJ. Anti-CCP antibodies: the past, the present and the future [review]. Nat Rev Rheumatol 2011;7:391-8.
Syversen SW, Gaarder PI, Goll GL, Odegard S, Haavardsholm EA, Mowinckel P, et al. High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 2008;67:212-7.
Lindqvist E, Eberhardt K, Bendtzen K, Heinegard D, Saxne T. Prognostic laboratory markers of joint damage in rheumatoid arthritis. Ann Rheum Dis 2005;64:196-201.
Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G, et al. Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset. Ann Rheum Dis 2006;65:453-8.
Van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 2005;7:R949-58.
Miriovsky BJ, Michaud K, Thiele GM, O'Dell JR, Cannon GW, Kerr G, et al. Anti-CCP antibody and rheumatoid factor concentrations predict greater disease activity in men with rheumatoid arthritis. Ann Rheum Dis 2010;69:1292-7.
Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T, et al. The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the α- and β-chains of fibrin. J Immunol 2001;166:4177-84.
Takizawa Y, Suzuki A, Sawada T, Ohsaka M, Inoue T, Yamada R, et al. Citrullinated fibrinogen detected as a soluble citrullinated autoantigen in rheumatoid arthritis synovial fluids. Ann Rheum Dis 2006;65:1013-20.
Vossenaar ER, Despres N, Lapointe E, van der Heijden A, Lora M, Senshu T, et al. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res Ther 2004;6:R142-50.
Kinloch A, Tatzer V, Wait R, Peston D, Lundberg K, Donatien P, et al. Identification of citrullinated α-enolase as a candidate autoantigen in rheumatoid arthritis. Arthritis Res Ther 2005;7:R1421-9.
Tsuda R, Ozawa T, Kobayashi E, Hamana H, Taki H, Tobe K, et al. Monoclonal antibody against citrullinated peptides obtained from rheumatoid arthritis patients reacts with numerous citrullinated microbial and food proteins. Arthritis Rheumatol 2015;67:2020-31.
Burkhardt H, Sehnert B, Bockermann R, Engstrom A, Kalden JR, Holmdahl R. Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis. Eur J Immunol 2005;35:1643-52.
Brink M, Hansson M, Mathsson L, Jakobsson PJ, Holmdahl R, Hallmans G, et al. Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis. Arthritis Rheum 2013;65:899-910.
Elliott SE, Kongpachith S, Lingampalli N, Adamska JZ, Cannon BJ, Mao R, et al. Affinity maturation drives epitope spreading and generation of proinflammatory anti-citrullinated protein antibodies in rheumatoid arthritis. Arthritis Rheumatol 2018;70:1946-58.
Titcombe PJ, Wigerblad G, Sippl N, Zhang N, Shmagel AK, Sahlstrom P, et al. Pathogenic citrulline-multispecific B cell receptor clades in rheumatoid arthritis. Arthritis Rheumatol 2018;70:1933-45.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
Munenaga S, Ouhara K, Hamamoto Y, Kajiya M, Takeda K, Yamasaki S, et al. The involvement of C5a in the progression of experimental arthritis with Porphyromonas gingivalis infection in SKG mice. Arthritis Res Ther 2018;20:247.
Ho PP, Lee LY, Zhao X, Tomooka BH, Paniagua RT, Sharpe O, et al. Autoimmunity against fibrinogen mediates inflammatory arthritis in mice. J Immunol 2010;184:379-90.
Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet 2007;41:107-20.
Rombouts Y, Willemze A, van Beers JJ, Shi J, Kerkman PF, van Toorn L, et al. Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis. Ann Rheum Dis 2016;75:578-85.
Kempers AC, Hafkenscheid L, Scherer HU, Toes RE. Variable domain glycosylation of ACPA-IgG: a missing link in the maturation of the ACPA response [review]? Clin Immunol 2018;186:34-7.
Scherer HU, Huizinga TWJ, Kronke G, Schett G, Toes RE. The B cell response to citrullinated antigens in the development of rheumatoid arthritis [review]. Nat Rev Rheumatol 2018;14:157-69.
Kuhn KA, Kulik L, Tomooka B, Braschler KJ, Arend WP, Robinson WH, et al. Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J Clin Invest 2006;116:961-73.
Sakaguchi N, Takahashi T, Hata H, Nomura T, Tagami T, Yamazaki S, et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 2003;426:454-60.
Yoshitomi H, Sakaguchi N, Kobayashi K, Brown GD, Tagami T, Sakihama T, et al. A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice. J Exp Med 2005;201:949-60.
Sato K, Takayanagi H. Osteoclasts, rheumatoid arthritis, and osteoimmunology. Curr Opin Rheumatol 2006;18:419-26.
Narazaki M, Tanaka T, Kishimoto T. The role and therapeutic targeting of IL-6 in rheumatoid arthritis [review]. Expert Rev Clin Immunol 2017;13:535-51.
Zhao X, Okeke NL, Sharpe O, Batliwalla FM, Lee AT, Ho PP, et al. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis. Arthritis Res Ther 2008;10:R94.
Sanchez-Pernaute O, Filkova M, Gabucio A, Klein M, Maciejewska-Rodrigues H, Ospelt C, et al. Citrullination enhances the proinflammatory response to fibrin in rheumatoid arthritis synovial fibroblasts. Ann Rheum Dis 2013;72:1400-6.
Hill JA, Bell DA, Brintnell W, Yue D, Wehrli B, Jevnikar AM, et al. Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice. J Exp Med 2008;205:967-79.
Sebbag M, Moinard N, Auger I, Clavel C, Arnaud J, Nogueira L, et al. Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins. Eur J Immunol 2006;36:2250-63.
Lunardi C, Bason C, Leandri M, Navone R, Lestani M, Millo E, et al. Autoantibodies to inner ear and endothelial antigens in Cogan's syndrome. Lancet 2002;360:915-21.
De Re V, Sansonno D, Simula MP, Caggiari L, Gasparotto D, Fabris M, et al. HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed cryoglobulinemia and B-cell clonal proliferations. Leukemia 2006;20:1145-54.
Kirvan CA, Cox CJ, Swedo SE, Cunningham MW. Tubulin is a neuronal target of autoantibodies in Sydenham's chorea. J Immunol 2007;178:7412-21.
Lundberg K, Wegner N, Yucel-Lindberg T, Venables PJ. Periodontitis in RA-the citrullinated enolase connection [review]. Nat Rev Rheumatol 2010;6:727-30.
Steen J, Forsström B, Sahlström P, Odowd V, Israelsson L, Krishnamurthy A, et al. Recognition of amino acid motifs, rather than specific proteins, by human plasma cell-derived monoclonal antibodies to posttranslationally modified proteins in rheumatoid arthritis. Arthritis Rheumatol 2019;71:196-209.
Li S, Yu Y, Yue Y, Liao H, Xie W, Thai J, et al. Autoantibodies from single circulating plasmablasts react with citrullinated antigens and porphyromonas gingivalis in rheumatoid arthritis. Arthritis Rheumatol 2016;68:614-26.
Takei M, Mitamura K, Fujiwara S, Horie T, Ryu J, Osaka S, et al. Detection of Epstein-Barr virus-encoded small RNA 1 and latent membrane protein 1 in synovial lining cells from rheumatoid arthritis patients. Int Immunol 1997;9:739-43.
Saal JG, Krimmel M, Steidle M, Gerneth F, Wagner S, Fritz P, et al. Synovial Epstein-Barr virus infection increases the risk of rheumatoid arthritis in individuals with the shared HLA-DR4 epitope. Arthritis Rheum 1999;42:1485-96.
Pratesi F, Tommasi C, Anzilotti C, Chimenti D, Migliorini P. Deiminated Epstein-Barr virus nuclear antigen 1 is a target of anti-citrullinated protein antibodies in rheumatoid arthritis. Arthritis Rheum 2006;54:733-41.
Panush RS, Stroud RM, Webster EM. Food-induced (allergic) arthritis: inflammatory arthritis exacerbated by milk. Arthritis Rheum 1986;29:220-6.
Panush RS. Food induced ("allergic") arthritis: clinical and serologic studies [letter]. J Rheumatol 1990;17:291-4.
Moen K, Brun JG, Valen M, Skartveit L, Eribe EK, Olsen I, et al. Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs. Clin Exp Rheumatol 2006;24:656-63.
Wegner N, Lundberg K, Kinloch A, Fisher B, Malmstrom V, Feldmann M, et al. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis [review]. Immunol Rev 2010;233:34-54.
Benckert J, Schmolka N, Kreschel C, Zoller MJ, Sturm A, Wiedenmann B, et al. The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific. J Clin Invest 2011;121:1946-55.
Czerkinsky C, Prince SJ, Michalek SM, Jackson S, Russell MW, Moldoveanu Z, et al. IgA antibody-producing cells in peripheral blood after antigen ingestion: evidence for a common mucosal immune system in humans. Proc Natl Acad Sci U S A 1987;84:2449-53.
Kokkonen H, Mullazehi M, Berglin E, Hallmans G, Wadell G, Ronnelid J, et al. Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis. Arthritis Res Ther 2011;13:R13.
Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E. 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;171:538-41.