TNF-alpha and IL-17 cytokine levels in Brazilian patients with ankylosing spondylitis after anti-TNF therapy

Authors

  • Fernanda Formaggi Lara-Armi Post Graduation Program in Biosciences and Phisiophatology, State University of Maringá, Maringá, PR, Brazil https://orcid.org/0000-0002-8776-1210
  • Jeane Eliete Laguila Visentainer Post Graduation Program in Biosciences and Phisiophatology, State University of Maringá, Maringá, PR, Brazil Professor, Department of Basic Health Sciences, State University of Maringá, Maringá, PR, Brazil
  • Matheus Braga Post Graduation Program in Biosciences and Phisiophatology, State University of Maringá, Maringá, PR, Brazil https://orcid.org/0000-0002-6316-4200
  • Joana Maira Valentini Zacarias Professor, Department of Basic Health Sciences, State University of Maringá, Maringá, PR, Brazil
  • Marco Antônio Rocha-Loures Department of Medicine, State University of Maringá, Maringá, PR, Brazil
  • Janisleya Silva Ferreira Neves Post Graduation Program in Biosciences and Phisiophatology, State University of Maringá, Maringá, PR, Brazil
  • Ricardo Alberto Moliterno Professor, Department of Basic Health Sciences, State University of Maringá, Maringá, PR, Brazil
  • Ana Maria Sell Post Graduation Program in Biosciences and Phisiophatology, State University of Maringá, Maringá, PR, Brazil Professor, Department of Basic Health Sciences, State University of Maringá, Maringá, PR, Brazil

DOI:

https://doi.org/10.1590/

Keywords:

Genetic association studies., Polymorphism;, genetic., Spondylitis;, ankylosing., Cytokines

Abstract

The aim of this study was to evaluate tumor necrosis factor alpha (TNF-α), interleukin (IL)- 17A/F levels in the serum of ankylosing spondylitis (AS) patients after anti-TNF therapy, in order to understand how these cytokines are involved in this therapeutic response. Forty-four AS patients were included in the study: thirty using anti-TNF therapy were classified according to their therapy response as responders (15) and non-responders (15) and 14 without anti-TNF therapy were classified as AS control. Fifteen healthy individuals formed the control group. Serum levels of TNF-α were determined using Luminex technology and for IL-17A and IL-17F using ELISA. The non-responder patients presented higher serum levels of TNF-α than the responders and AS control; the same results were found when HLA-B*27 positive or negative patients were separately analyzed. IL-17A and IL17F serum levels were similar for all groups. According to the clinical disease activity, AS patients with BASDAI ≥4 had higher serum levels of TNF-α than AS patients with BASDAI <4. Positive correlation was found between TNF-α levels and BASDAI. In AS patients, TNF-α serum levels were associated with anti-TNF therapy and disease activity independently of HLA-B*27, and IL-17A and IL-17F were not related to anti-TNF treatment.

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References

Abraham LJ, Kroeger KM. Impact of the -308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease. J Leukoc Biol. 1999;66(4):562-6.

Banday MZ, Balkhi HM, Hamid Z, Sameer AS, Chowdri NA, Haq E. Tumor necrosis factor-α (TNF-α)-308G/A promoter polymorphism in colorectal cancer in ethnic Kashmiri population - A case control study in a detailed perspective. Meta Gene. 2016;9:128-36.

Braga M, Lara-Armi FF, Neves JSF, Rocha-Loures MA, Terron-Monich MS, Bahls-Pinto LD, et al. Influence of IL10 (rs1800896) Polymorphism and TNF-α, IL-10, IL- 17A, and IL-17F Serum Levels in Ankylosing Spondylitis. Front Immunol. 2021;12:653611.

Braun J, Baraliakos X, Deodhar A, Baeten D, Sieper J, Emery P, et al. Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheum Dis. 2017;76(6):1070-7.

Costantino F, Breban M, Garchon HJ. Genetics and Functional Genomics of Spondyloarthritis. Front Immunol . 2018;18;9:2933.

Espinoza JL, Takami A, Nakata K, Onizuka M, Kawase T, Akiyama H, et al. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation. PLoS One. 2011;6(10):e26229.

Gonzalez-Lopez L, Fajardo-Robledo NS, Miriam Saldaña-Cruz A, Moreno-Sandoval IV, Bonilla-Lara D, Zavaleta-Muñiz S, et al. Association of adipokines, interleukin-6, and tumor necrosis factor-α concentrations with clinical characteristics and presence of spinal syndesmophytes in patients with ankylosing spondylitis: A cross-sectional study. J Int Med Res. 2017;45(3):1024-35.

Kawaguchi M, Takahashi D, Hizawa N, Suzuki S, Matsukura S, Kokubu F, et al. IL-17F sequence variant (His161Arg) is associated with protection against asthma and antagonizes wild-type IL-17F activity. J Allergy Clin Immunol. 2006;117(4):795-801.

Kroeger KM, Steer JH, Joyce DA, Abraham LJ. Effects of stimulus and cell type on the expression of the -308 tumour necrosis factor promoter polymorphism. Cytokine. 2000;12(2):110-9.

Lara-Armi FF, Visentainer JEL, Alves HV, Rocha-Loures MA, Neves JSF, Colli CM, et al. Optimization of HLA-B*27 ALLELE Genotyping by PCR-SSP. Clinics (Sao Paulo). 2020;75:e1840.

Lata M, Hettinghouse AS, Liu CJ. Targeting tumor necrosis factor receptors in ankylosing spondylitis. Ann N Y Acad Sci. 2019;1442(1):5-16.

Limón-Camacho L, Vargas-Rojas MI, VÁZquez-Mellado J, Casasola-Vargas J, Moctezuma JF, Burgos-Vargas R, et al. In Vivo Peripheral Blood Proinflammatory T Cells in Patients with Ankylosing Spondylitis. J Rheumatol. 2012;39(4):830.

Menegatti S, Bianchi E, Rogge L. Anti-TNF Therapy in Spondyloarthritis and Related Diseases, Impact on the Immune System and Prediction of Treatment Responses. Front Immunol . 2019;10:382: 1-29.

Milanez FM, Saad CGS, Viana VT, Moraes JCB, Périco GV, Sampaio-Barros PD, et al. IL-23/Th17 axis is not influenced by TNF-blocking agents in ankylosing spondylitis patients. Arthritis Res Ther. 2016;18:52.

Park MC, Lee SW, Choi ST, Park YB, Lee SK. Serum leptin levels correlate with interleukin-6 levels and disease activity in patients with ankylosing spondylitis. Scand J Rheumatol . 2007;36(2):101-6.

Pedersen SJ, Maksymowych WP. Beyond the TNF-α Inhibitors: New and Emerging Targeted Therapies for Patients with Axial Spondyloarthritis and their Relation to Pathophysiology. Drugs. 2018;78(14):1397-418.

Probst CM, Bompeixe EP, Pereira NF, de ODMM, Visentainer JE, Tsuneto LT, et al. HLA polymorphism and evaluation of European, African, and Amerindian contribution to the white and mulatto populations from Parana, Brazil. Hum Biol. 2000;72(4):597-617.

Ranganathan V, Gracey E, Brown MA, Inman RD, Haroon N. Pathogenesis of ankylosing spondylitis - recent advances and future directions. Nat Rev Rheumatol. 2017;13(6):359-67.

Reis PG, Ambrosio-Albuquerque EP, Fabreti-Oliveira RA, Moliterno RA, de Souza VH, Sell AM, et al. HLA-A, -B, -DRB1, -DQA1, and -DQB1 profile in a population from southern Brazil. Hla. 2018;92(5):298-303.

Rocha Loures MA, Macedo LC, Reis DM, Oliveira CF, Meneguetti JL, Martines GF, et al. Influence of TNF and IL17 Gene Polymorphisms on the Spondyloarthritis Immunopathogenesis, Regardless of HLA-B27, in a Brazilian Population. Mediators Inflamm. 2018;2018:1395823.

Rubbert-Roth A, Atzeni F, Masala IF, Caporali R, Montecucco C, Sarzi-Puttini P. TNF inhibitors in rheumatoid arthritis and spondyloarthritis: Are they the same? Autoimmun Rev. 2018;17(1):24-8.

Rudwaleit M, van der Heijde D, Landewé R, Akkoc N, Brandt J, Chou CT, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis . 2011;70(1):25-31.

Rudwaleit M, Van Der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis . 2009;68(6):777-83.

Ruiz de Morales JMG, Puig L, Dauden E, Canete JD, Pablos JL, Martin AO, et al. Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies. Autoimmun Rev . 2020;19(1):102429.

Torres TM, Ciconelli RM. Instrumentos de avaliação em espondilite anquilosante. Rev Bras Reumatol. 2006;46:52-9.

Tutuncu ZN, Bilgie A, Kennedy LG, Calin A. Interleukin-6, acute phase reactants and clinical status in ankylosing spondylitis. Ann Rheum Dis . 1994;53(6):425-6.

Weiskopf D, Birgit W, Grubeck‐Loebenstein B. The aging of the immune system. Transpl Int. 2009;22(11):1041-1050.

Vecellio M, Cohen CJ, Roberts AR, Wordsworth PB, Kenna TJ. RUNX3 and T-Bet in Immunopathogenesis of Ankylosing Spondylitis-Novel Targets for Therapy? Front Immunol . 2019;10;9:3132.

Wen JT, Zhang DH, Fang PF, Li MH, Wang RJ, Li SH. Role of Th1/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondylitis. Genet Mol Res. 2017;16(1).

Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A. 1997;94(7):3195-9.

Xueyi L, Lina C, Zhenbiao W, Qing H, Qiang L, Zhu P. Levels of circulating Th17 cells and regulatory T cells in ankylosing spondylitis patients with an inadequate response to anti-TNF-α therapy. J Clin Immunol. 2013;33(1):151-61.

Zacarias JM, Sippert EÂ, Tsuneto PY, Visentainer JE, de Oliveira e Silva C, Sell AM. The Influence of Interleukin 17A and IL17F Polymorphisms on Chronic Periodontitis Disease in Brazilian Patients. Mediators Inflamm . 2015;2015:147056.

Zhu W, He X, Cheng K, Zhang L, Chen D, Wang X, et al. Ankylosing spondylitis: etiology, pathogenesis, and treatments. Bone Res. 2019;7:22.

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Published

2023-11-03

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How to Cite

TNF-alpha and IL-17 cytokine levels in Brazilian patients with ankylosing spondylitis after anti-TNF therapy. (2023). Brazilian Journal of Pharmaceutical Sciences, 59, 18. https://doi.org/10.1590/