Assessment of serum TWEAK levels in patients with familial Mediterranean fever
Keywords:
Familial Mediterranean Fever, TWEAK, inflammation, BiomarkerAbstract
Background/Aim: Mediterranean fever is an autoinflammatory disease characterized by recurrent attacks. Tumor necrosis factor (TNF) - like weak inducer of apoptosis (TWEAK) is a member of the TNF ligand family, and it has been reported to contribute significantly to the initiation of many inflammatory and immunological processes. In previous studies, an increasing amount of evidence has implicated the participation of TWEAK / Fn14 pathway in the pathogenesis of rheumatic inflammatory diseases that include rheumatoid arthritis, systemic lupus erythematosus and Behçet's disease. The aim of this study was to investigate the serum TWEAK levels of patients with Familial Mediterranean fever (FMF) and its possible relationship with inflammatory markers and disease activity. Methods: Our study included 20 patients with FMF and 19 healthy volunteers. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were measured, and PRAS disease severity score was determined in patients with FMF. Also, the FMF attack period was questioned. Serum TWEAK levels were measured with available commercial Enzyme Linked Immunosorbent Assay kits. Results: There was no significant difference in terms of age and gender between the FMF group and the healthy control group (P>0.05, for all). ESR, CRP and serum TWEAK levels were significantly higher in patients with FMF (P<0.001 for all). PRAS score in FMF patients was 3.4. Serum TWEAK level was not correlated with ESR (r=-0.042, P=0.0801), CRP (r=-0.017 P=0.921), or PRAS score (r=0.247, P=0.149). The ESR and CRP levels of patients in FMF attack period were significantly higher compared to attack free period (P<0.001 for both) whereas there was no significant difference in serum TWEAK levels (P=0.686). Conclusions: Serum TWEAK levels are increased in FMF disease with attacks. However, this increase is not associated with increased ESR and CRP during FMF attacks. These results indicate that the TWEAK / Fn14 pathway plays a role in earlier stages where the inflammatory pathways have not differentiated yet. Serum TWEAK levels appear to be more successful in reflecting a lower degree of inflammation compared to ESR and CRP.
Downloads
References
Rigante D. A developing portrait of hereditary periodic fevers in childhood. Expert Opinion on Orphan Drugs. 2018;6(1):47-55.
Kehribar DY, Özgen M.The importance of Mediterranean fever gene in familial Mediterranean fever. Eur J Rheumatol. 2020;7:173-6
Kehribar DY, Özgen M. Efficacy of anti-interleukin-1 treatment in colchicine-resistant arthritis in patients with familial Mediterranean fever. Eur J Rheumatol. 2020 Sep 18. doi: 10.5152/eurjrheum.2020.20126
Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, et al. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol. 2015;4:296-307. doi: 10.1016/j.redox.2015.01.008
The French FMF Consortium. A candidate gene for familial mediterranean fever.Nat Genet. 1997;17(1):25-31. doi: 10.1038/ng0997-25
Franchi L, Eigenbröd T, Munoz-Planillo R, Nurez G. The inflammasome; a caspase-1- activation platform that regulates immune response and disease pathogenesis. Nat Immunol. 2009;10(3):241-7. doi: 10.1038/ni.1703.
Papin S, Cuenin S, Agostini L, Martinon F, Werner S, Beer H-D, et al. The SPRY domain of pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1 beta processing. Cell Death Differ. 2007;14(8):1457-66. doi: 10.1038/sj.cdd.4402142.
Roos C, Wicovsky A, Müller N, Salzmann S, Rosenthal T, Kalthoff H, et al. Soluble and transmembrane TNF-like weak inducer of apoptosis differentially activate the classical and noncanonical NF-kappa B pathway. J Immun. 2010;3:1593-695.
Chicheportiche Y, Bourdon PR, Xu H, Hsu YM, Scott H, Hession C, et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem. 1997;272:32401-10.
Xia Y, Herlitz LC, Gindea S, Wen J, Pawar RD, Misharin A, et al. Deficiency of fibroblast growth factor-inducible 14 (Fn14) preserves the filtration barrier and ameliorates lupus nephritis. J Am Soc Nephrol. 2015;5:1053-70.
Xia WY, Stock A, Michaelson JS, Burkly LC, Gulinello M, Putterman C, et al. Neuropsychiatric disease in murine lupus is dependent on the TWEAK/Fn14 pathway. J Autoimmun. 2013;43:44-54.
Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov. 2008;7:411-25.
Zimmermann M, Koreck A, Meyer N, Basinski T, Meiler F, Simone B, et al. TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis. J Allergy Clin Immunol. 2011;1:200-7.
Burkly LC, Michaelson JS, Hahm K, Jakubowski A, Zheng TS. TWEAKing tissue remodeling by a multifunctional cytokine: role of TWEAK/Fn14 pathway in health and disease. Cytokine. 2007;40:1-16.
Madrigal-Matute J, Fernandez-Laso V, Sastre C, Llamas-Granda P, Egido J, Ventura MJL, et al. TWEAK/Fn14 interaction promotes oxidative stress through NADPH oxidase activation in macrophages. Cardiovasc Res. 2015;1:139-47.
Wisniacki N, Amaravadi L, Galluppi GR, Zheng TS, Zhang R, Kong J, Burkly LC. Safety, tolerability, pharmacokinetics, and pharmacodynamics of anti-TWEAK monoclonal antibody in patients with rheumatoid arthritis. Clin Ther. 2013;35:1137-49.
Sun F, Teng J, Yu P, Li W, Chang J, Xu H. Involvement of TWEAK and the NF-κB signaling pathway in lupus nephritis. Exp Ther Med. 2018;15:2611-9.
Panezai J, Ali A, Ghaffar A, Benchimol D, Altamash M, Klinge B, et al. Upregulation of circulating inflammatory biomarkers under the influence of periodontal disease in rheumatoid arthritis patients. Cytokine 2020;131:155117.
Chen J, Jia F, Ren K, Luo M, Min X, Wang P, et al. Inhibition of suppressor of cytokine signaling 1 mediates the profibrotic effect of TWEAK/Fn14 signaling on kidney cells. Cell Signal. 2020;71:109615.
Kehribar DY, Cihangiroğlu M, Sehmen E, Avci B, Çapraz M, Boran M, et al. The assessment of the serum levels of TWEAK and prostaglandin F2alpha in COVID - 19. Turk J Med Sci. 2020 Sep 27. doi: 10.3906/sag-2006-96.
Kehribar DY, Özgen M. Clinical Features of Patients with Vascular Involvement in Behçet’s Disease Tepecik Eğit. ve Araşt. Hast. Dergisi. 2020;30(2):122-6.
Kehribar DY, Ozgen M. Infliximab treatment in refractory vascular Behcet's disease: A single-center experience. Vascular. 2020;28(6):829-33.
Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997; 40: 1879-85.
Van Kuijk AW, Wijbrandts CA, Vinkenoog M, Zheng TS, Reedquist KA, Tak PP. TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to TNF blockade. Ann Rheum Dis. 2009;69:301-4.
Kamata K, Kmaijo S, Nakajima A, Koyanagi A, Kurosawa H, Yagita H, et al. Involvement of TNF-like WEAK inducer of apoptosis in the pathogenesis of collagen-induced arthritis. J Immunol. 2006;177:6433-9.
Wisniacki N, Amaravadi L, Galluppi GR, Zheng TS, Zhang R, Kong J, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of anti-TWEAK monoclonal antibody in patients with rheumatoid arthritis. Clin Ther. 2013;35:1137-49.
Reyes-Martinez F, Pérez-Navarro M, Rodriguez-Matias A, Virgilia Soto-Abraham V, Gutierrez-Reyes G, Medina-Avila Z, et al. Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: an exploratory study. Nefrologia. 2018;38:152-60.
Choe JY, Kim SK. Serum TWEAK as a biomarker for disease activity of systemic lupus erythematosus. Inflamm Res. 2016;65:479-88.
Schwartz N, Michaelson JS, Putterman C. Lipocalin-2, TWEAK, and other cytokines as urinary biomarkers for lupus nephritis. Ann N Y Acad Sci. 2007;1109:265-74.
Maarouf A, Stephan D, Ranjeva MP, Ranjeva JP, Pelletier J, Audoin B, et al. High levels of serum soluble TWEAK are associated with neuroinflammation during multiple sclerosis. J Transl Med. 2019;17:51.
Grimstad T, Skoie IM, Doerner J, Isaksen K, Karlsen L, Aabakken L, et al. TWEAK is not elevated in patients with newly diagnosed inflammatory bowel disease. J Gastroenterol. 2017;52:420-4.
Downloads
- 331 579
Published
Issue
Section
How to Cite
License
Copyright (c) 2021 Gökhan Yavuzbilge, Muhammed Okuyucu, Yeşim Civil, Serkan Günaydın, Bahattin Avcı
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.