Abstract
Introduction
Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects small joints. The impaired chemokine and cytokine responses are essential pathological mechanisms for the RA clinical presentation. Given the role of chemokines and inflammatory reactions in RA pathogenesis, we evaluate the association between the plasma concentration of CCL20 with the clinical and laboratory parameters in newly diagnosed RA patients.
Material and methods
Forty-five newly diagnosed RA patients and forty-five healthy subjects were enrolled in this study. The plasma levels of CCL20, rheumatoid factor, and anti-citrullinated peptide antibodies were measured using the enzyme-linked immunosorbent assay (ELISA) technique.
Result
The plasma levels of CCL20 were increased significantly in RA patients compared to the healthy controls (p < 0.0001). There was a positive correlation between CCL20 and RF, anti-CCP, ESR, and DAS-28 (p < 0.0001, r = 0.669; p < 0.015, r = 0.358; p < 0.0001, r = 0.586; p < 0.0001, r = 0.769).
Conclusion
The increased plasma levels of CCL20 in newly diagnosed RA patients may contribute to RA pathogenesis, and it is in association with clinical and laboratory parameters.
Key Points • CCL20 has a contribution to the early phase of RA. |
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References
Holmdahl R, Malmström V, Burkhardt H (2014) Autoimmune priming, tissue attack and chronic inflammation—the three stages of rheumatoid arthritis. Eur J Immunol 44(6):1593–1599
McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365(23):2205–2219
Choy E (2012) Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology 51(suppl_5):v3–v11
Picerno V, Ferro F, Adinolfi A, Valentini E, Tani C, Alunno A (2015) One year in review: the pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol 33(4):551–558
McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7(6):429–442
Chen S-J, Lin G-J, Chen J-W, Wang K-C, Tien C-H, Hu C-F et al (2019) Immunopathogenic mechanisms and novel immune-modulated therapies in rheumatoid arthritis. Int J Mol Sci 20(6):1332
Koch AE (2005) Chemokines and their receptors in rheumatoid arthritis: future targets? Arthritis Rheum 52:710–721
Szekanecz Z, Kim J, Koch AE (2003) Chemokines and chemokine receptors in rheumatoid arthritis. Semin Immunol 15(1):15–21
Ruth J, Morel J, Park C, Kumar P, Koch A. 2000 MIP-3 alpha expression in the rheumatoid joint. Arthritis and rheumatism: Lippincott Williams & Wilkins 530 Walnut St, Philadelphia, PA 19106–3621 USA;. p. S78-S.
Page G, Lebecque S, Miossec P (2002) Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ: correlation with selective chemokine expression in rheumatoid synovium. J Immunol 168(10):5333–5341
Matsui T, Akahoshi T, Namai R, Hashimoto A, Kurihara Y, Rana M et al (2001) Selective recruitment of CCR6-expressing cells by increased production of MIP-3α in rheumatoid arthritis. Clin Exp Immunol 125(1):155–161
Vervoordeldonk MJ, Tak PP (2002) Cytokines in rheumatoid arthritis. Curr Rheumatol Rep 4(3):208
Navegantes KC, de Souza GR, Pereira PAT, Czaikoski PG, Azevedo CHM, Monteiro MC (2017) Immune modulation of some autoimmune diseases: the critical role of macrophages and neutrophils in the innate and adaptive immunity. J Transl Med 15(1):1–21
Peiris J, Gordon S, Unkeless J, Porterfield J (1981) Monoclonal anti-Fc receptor IgG blocks antibody enhancement of viral replication in macrophages. Nature 289(5794):189–191
Greiner A, Plischke H, Kellner H, Gruber R (2005) Association of anti-cyclic citrullinated peptide antibodies, anti-citrullin antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis. Ann N Y Acad Sci 1050(1):295–303
Lingampalli N, Sokolove J, Lahey LJ, Edison JD, Gilliland WR, Holers VM et al (2018) Combination of anti-citrullinated protein antibodies and rheumatoid factor is associated with increased systemic inflammatory mediators and more rapid progression from preclinical to clinical rheumatoid arthritis. Clin Immunol 195:119–126
Kurowska W, Kuca-Warnawin EH, Radzikowska A, Maśliński W (2017) The role of anti-citrullinated protein antibodies (ACPA) in the pathogenesis of rheumatoid arthritis. Cent Eur J Immunol 42(4):390
Harrold LR, Shan Y, Connolly SE, Alemao E, Rebello S, Guo L et al (2020) Association among anti-citrullinated protein antibody status, erosive disease and healthcare resource utilization in patients with rheumatoid arthritis. Curr Med Res Opin 36(2):337–342
Pelletier M, Maggi L, Micheletti A, Lazzeri E, Tamassia N, Costantini C et al (2010) Evidence for a cross-talk between human neutrophils and Th17 cells. Blood 115(2):335–343
Kay J, Upchurch KS (2012) ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology 51(suppl_6):vi5–vi9
Elemam NM, Hannawi S, Maghazachi AA (2020) Role of chemokines and chemokine receptors in rheumatoid arthritis. ImmunoTargets and Therapy 9:43
Crijns H, Vanheule V, Proost P (2020) Targeting chemokine—glycosaminoglycan interactions to inhibit inflammation. Front Immunol 11:483
Harlow L, Rosas IO, Gochuico BR, Mikuls TR, Dellaripa PF, Oddis CV et al (2013) Identification of citrullinated Hsp90 isoforms as novel autoantigens in rheumatoid arthritis–associated interstitial lung disease. Arthritis Rheum 65(4):869–879
Ruth JH, Shahrara S, Park CC, Morel JC, Kumar P, Qin S et al (2003) Role of macrophage inflammatory protein-3α and its ligand CCR6 in rheumatoid arthritis. Lab Invest 83(4):579–588
Kawashiri S-Y, Kawakami A, Iwamoto N, Fujikawa K, Aramaki T, Tamai M et al (2009) Proinflammatory cytokines synergistically enhance the production of chemokine ligand 20 (CCL20) from rheumatoid fibroblast-like synovial cells in vitro and serum CCL20 is reduced in vivo by biologic disease-modifying antirheumatic drugs. J Rheumatol 36(11):2397–2402
Kageyama Y, Ichikawa T, Nagafusa T, Torikai E, Shimazu M, Nagano A (2007) Etanercept reduces the serum levels of interleukin-23 and macrophage inflammatory protein-3 alpha in patients with rheumatoid arthritis. Rheumatol Int 28(2):137–143
Meitei HT, Jadhav N, Lal G (2021) CCR6-CCL20 axis as a therapeutic target for autoimmune diseases. Autoimmun Rev 20(7):102846
Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N et al (2007) Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 204(12):2803–2812
Kulkarni N, Meitei HT, Sonar SA, Sharma PK, Mujeeb VR, Srivastava S et al (2018) CCR6 signaling inhibits suppressor function of induced-Treg during gut inflammation. J Autoimmun 88:121–130
Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM (2001) T cell activation in rheumatoid synovium is B cell dependent. J Immunol 167(8):4710–4718
Rantapää-Dahlqvist S, De Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H et al (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48(10):2741–2749
Seegobin SD, Ma MH, Dahanayake C, Cope AP, Scott DL, Lewis CM et al (2014) ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial. Arthritis Res Ther 16(1):R13
Acknowledgements
We thankfully acknowledge the deputy of research and technology of the Kermanshah University of Medical Sciences for financial support of this work.
Funding
This work was supported by the Kermanshah University of Medical Sciences grant number (3010723).
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M.T. was involved in the concept and design of the study. P.F. drafted the manuscript. All authors were involved in acquiring, analyzing, and interpreting the data and approved the final version.
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Pournazari, M., Feizollahi, P., Roghani, S.A. et al. Increased plasma levels of CCL20 in peripheral blood of rheumatoid arthritis patients and its association with clinical and laboratory parameters. Clin Rheumatol 41, 265–270 (2022). https://doi.org/10.1007/s10067-021-05899-x
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DOI: https://doi.org/10.1007/s10067-021-05899-x