Özet
Familial Mediterranean fever (FMF) is a hereditary disease characterized by recurring, self-limited inflammatory episodes. The disease is caused by a gain-of-function mutation in MEFV (MEditerranean FeVer) gene, encoding pyrin protein, the key element of the pyrin inflammasome, resulting in excessive production of proinflammatory cytokines, namely IL-1β, IL-6 and IL-18. Innate immunity was thought to be the sole perpetrator in the chronic inflammation, however, contemporary research provided evidence of the role of adaptive immunity in inflammatory process. Spondyloarthropathies accompanying FMF consist of inflammatory arthritides, sacroiliitis, spondylitis, enthesitis and extraskeletal manifestations, in children classified as enthesitis relared arthritis (ERA). The pathogenesis of these conditions is unclear, however the common perception is that antigen-specific immune response with underlying chronic inflammation is the causative mechanism. In this study, chosen inflammatory marker levels are evaluated in order to gain further knowledge on the pathogenetic mechanisms of FMF and acompanying spondyloarthritis (SpA). Thus, we recruited the patients whose routine examinations were in between December 2020 and June 2021, creating four groups with FMF-SpA with high disease activity, ERA with high disease activity, FMF during attack period and FMF remission period. Having collected 20 samples, the inflammatory marker levels of these groups are compared with each disease group and the healthy donors. IL-18 levels are statistically significantly increased in FMF-SpA group, suggesting the chance to be an inflammatory biomarker for ERA/spondyloarthritides in the FMF group. TNF-α levels are increased in all the disease groups compared to healthy controls are statistically significant. This increment is validating the anti-TNF-α agents in the treatment of both FMF and ERA. The fact that IFN-α2 levels were unmeasurably low in the high disease activity groups in contrast to the healthy donors and FMF remission groups strengthens the theory of no type 1 IFN activity in these inflammatory pathways. Lastly, MCP-1 levels are significantly low in all the patient groups compared with the healthy controls. This study is the first to investigate the inflammatory pathogenesis of FMF and accompanying SpA in children and the fact that most of the inflammatory marker levels are comparable among the disease groups indicates that these entities share a common inflammatory pathway. Corroboratory studies are needed to further evaluate the role of these cytokines and their incorporation into personalized medicine.
Künye
1. Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, et al. Classification criteria for autoinflammatory recurrent fevers. Annals of the rheumatic diseases. 2019;78(8):1025-32.
2. Consortium IF. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell. 1997;90(4):797-807.
3. Dinarello CA. Interleukin-1β and the autoinflammatory diseases. Mass Medical Soc; 2009. p. 2467-70.
4. Schnappauf O, Chae JJ, Kastner DL, Aksentijevich I. The pyrin inflammasome in health and disease. Frontiers in immunology. 2019;10:1745.
5. Musabak U, Sengul A, Oktenli C, Pay S, Yesilova Z, Kenar L, et al. Does immune activation continue during an attack‐free period in familial Mediterranean fever? Clinical & Experimental Immunology. 2004;138(3):526-33.
6. Aypar E, Ozen S, Okur H, Kutluk T, Besbas N, Bakkaloglu A. Th1 polarization in familial Mediterranean fever. The Journal of rheumatology. 2003;30(9):2011-3.
7. Babaoglu H, Armagan B, Bodakci E, Satis H, Atas N, Sari A, et al. Factors associated with damage in patients with familial Mediterranean fever. Clin Exp Rheumatol. 2020;38(127):S42-S8.
8. Balcı-Peynircioğlu B, Kaya-Akça Ü, Arıcı ZS, Avcı E, Akkaya-Ulum ZY, Karadağ Ö, et al. Comorbidities in familial Mediterranean fever: analysis of 2000 genetically confirmed patients. Rheumatology. 2020;59(6):1372-80.
9. Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever: a survey of 470 cases and review of the literature. The American journal of medicine. 1967;43(2):227-53.
10. Debeljak M, Toplak N, Abazi N, Szabados B, Mulaosmanović V, Radović J, et al. The carrier rate and spectrum of MEFV gene mutations in central and southeastern European populations. Clin Exp Rheumatol. 2015;33(6 Suppl 94):S19-23.
11. Samuels J, Aksentijevich I, Torosyan Y, Centola M, Deng Z, Sood R, et al. Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine. 1998;77(4):268-97.
12. Ben-Chetrit E, Levy M. Familial mediterranean fever. The Lancet. 1998;351(9103):659-64.
13. Yalçınkaya F, Group TFS. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. 2005.
14. Ben‐Chetrit E, Touitou I. Familial Mediterranean fever in the world. Arthritis Care & Research. 2009;61(10):1447-53.
15. Yilmaz E, Ozen S, Balcı B, Duzova A, Topaloglu R, Besbas N, et al. Mutation frequency of familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. European journal of human genetics. 2001;9(7):553-5.
16. Rogers DB, Shohat M, Petersen GM, Bickal J, Congleton J, Schwabe AD, et al. Familial Mediterranean fever in Armenians: autosomal recessive inheritance with high gene frequency. American journal of medical genetics. 1989;34(2):168-72.
17. Gershoni-Baruch R, Shinawi M, Leah K, Badarnah K, Brik R. Familial Mediterranean fever: prevalence, penetrance and genetic drift. European Journal of Human Genetics. 2001;9(8):634-7.
18. Daniels M, Shohat T, Brenner‐Ullman A, Shohat M. Familial Mediterranean fever: high gene frequency among the non‐Ashkenazic and Ashkenazic Jewish populations in Israel. American journal of medical genetics. 1995;55(3):311-4.
19. Sarkisian T, Ajrapetian H, Beglarian A, Shahsuvarian G, Egiazarian A. Familial Mediterranean fever in Armenian population. Georgian Med News. 2008;156:105-11.
20. Chung LK, Park YH, Zheng Y, Brodsky IE, Hearing P, Kastner DL, et al. The Yersinia virulence factor YopM hijacks host kinases to inhibit type III effector-triggered activation of the pyrin inflammasome. Cell host & microbe. 2016;20(3):296-306.
21. Diaz A, Hu C, Kastner DL, Schaner P, Reginato AM, Richards N, et al. Lipopolysaccharide‐induced expression of multiple alternatively spliced MEFV transcripts in human synovial fibroblasts: a prominent splice isoform lacks the C‐terminal domain that is highly mutated in familial Mediterranean fever. Arthritis & Rheumatism. 2004;50(11):3679-89.
22. Mansfield E, Chae JJ, Komarow HD, Brotz TM, Frucht DM, Aksentijevich I, et al. The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments. Blood, The Journal of the American Society of Hematology. 2001;98(3):851-9.
23. Yu J-W, Fernandes-Alnemri T, Datta P, Wu J, Juliana C, Solorzano L, et al. Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Molecular cell. 2007;28(2):214-27.
24. Chae JJ, Aksentijevich I, Kastner DL. Advances in the understanding of familial Mediterranean fever and possibilities for targeted therapy. British journal of haematology. 2009;146(5):467-78.
25. Shinar Y, Obici L, Aksentijevich I, Bennetts B, Austrup F, Ceccherini I, et al. Guidelines for the genetic diagnosis of hereditary recurrent fevers. Annals of the rheumatic diseases. 2012;71(10):1599-605.
26. Schnappauf O, Chae JJ, Kastner DL, Aksentijevich I. The pyrin inflammasome in health and disease. Frontiers in immunology. 2019:1745.
27. SOHAR E, PRASS M, HELLER J, HELLER H. Genetics of familial Mediterranean fever (FMF): A disorder with recessive inheritance in non-Ashkenazi Jews and Armenians. Archives of Internal Medicine. 1961;107(4):529-38.
28. Chae JJ, Cho Y-H, Lee G-S, Cheng J, Liu PP, Feigenbaum L, et al. Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1β activation and severe autoinflammation in mice. Immunity. 2011;34(5):755-68.
29. Lachmann H, Şengül B, Yavuzşen T, Booth D, Booth S, Bybee A, et al. Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology. 2006;45(6):746-50.
30. Ozen S, Bakkaloglu A, Yilmaz E, Duzova A, Balci B, Topaloglu R, et al. Mutations in the gene for familial Mediterranean fever: do they predispose to inflammation? The Journal of rheumatology. 2003;30(9):2014-8.
31. Touitou I. The spectrum of familial Mediterranean fever (FMF) mutations. European Journal of Human Genetics. 2001;9(7):473-83.
32. Kelesoglu FM, Aygun E, Okumus NK, Ersoy A, Karapınar E, Saglam N, et al. Evaluation of subclinical inflammation in familial Mediterranean fever patients: relations with mutation types and attack status: a retrospective study. Clinical rheumatology. 2016;35(11):2757-63.
33. Grossman C, Kassel Y, Livneh A, Ben-Zvi I. Familial Mediterranean fever (FMF) phenotype in patients homozygous to the MEFV M694V mutation. European journal of medical genetics. 2019;62(6):103532.
34. Lidar M, Yonath H, Shechter N, Sikron F, Sadetzki S, Livneh A, et al. Incomplete response to colchicine in M694V homozygote FMF patients. Autoimmunity reviews. 2012;12(1):72-6.
35. Ait-Idir D, Khilan A, Djerdjouri B, El-Shanti H. Spectrum of mutations and carrier frequency of familial Mediterranean fever gene in the Algerian population. Rheumatology. 2011;50(12):2306-10.
36. Touitou I, Sarkisian T, Medlej‐Hashim M, Tunca M, Livneh A, Cattan D, et al. Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis & Rheumatism. 2007;56(5):1706-12.
37. Gangemi S, Manti S, Procopio V, Casciaro M, Di Salvo E, Cutrupi M, et al. Lack of clear and univocal genotype‐phenotype correlation in familial Mediterranean fever patients: A systematic review. Clinical genetics. 2018;94(1):81-94.
38. Gkretsi V, Deltas C, Yapijakis C, Lamnissou K. Screening for familial Mediterranean fever M694V and V726A mutations in the Greek population. Genetic testing and molecular biomarkers. 2009;13(3):291-3.
39. Topaloglu R, Batu ED, Yıldız Ç, Korkmaz E, Özen S, Beşbaş N, et al. Familial Mediterranean fever patients homozygous for E148Q variant may have milder disease. International journal of rheumatic diseases. 2018;21(10):1857-62.
40. Arici ZS, Romano M, Piskin D, Guzel F, Sahin S, Berard RA, et al. Evaluation of E148Q and Concomitant AA Amyloidosis in Patients with Familial Mediterranean Fever. Journal of Clinical Medicine. 2021;10(16):3511.
41. Aydın F, Çakar N, Özçakar ZB, Uncu N, Başaran Ö, Özdel S, et al. Clinical features and disease severity of Turkish FMF children carrying E148Q mutation. Journal of clinical laboratory analysis. 2019;33(4):e22852.
42. Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E, Giancane G, et al. EULAR recommendations for the management of familial Mediterranean fever. Annals of the rheumatic diseases. 2016;75(4):644-51.
43. Booty MG, Chae JJ, Masters SL, Remmers EF, Barham B, Le JM, et al. Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 2009;60(6):1851-61.
44. Federici S, Calcagno G, Finetti M, Gallizzi R, Meini A, Vitale A, et al. Clinical impact of MEFV mutations in children with periodic fever in a prevalent western European Caucasian population. Annals of the rheumatic diseases. 2012;71(12):1961-5.
45. Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med. 2007;65(9):318-24.
46. Özen S. Changing concepts in familial mediterranean fever: Is it possible to have an autosomal‐recessive disease with only one mutation? : Wiley Online Library; 2009.
47. McDermott MF, Aksentijevich I. The autoinflammatory syndromes. Current opinion in allergy and clinical immunology. 2002;2(6):511-6.
48. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428-35.
49. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140(6):771-6.
50. de Torre-Minguela C, Mesa del Castillo P, Pelegrín P. The NLRP3 and pyrin inflammasomes: implications in the pathophysiology of autoinflammatory diseases. Frontiers in immunology. 2017;8:43.
51. Pelegrín P. Inflammasome activation by danger signals. The Inflammasomes: Springer; 2011. p. 101-21.
52. Ratsimandresy RA, Dorfleutner A, Stehlik C. An update on PYRIN domain-containing pattern recognition receptors: from immunity to pathology. Frontiers in immunology. 2013;4:440.
53. Seshadri S, Duncan MD, Hart JM, Gavrilin MA, Wewers MD. Pyrin levels in human monocytes and monocyte-derived macrophages regulate IL-1β processing and release. The Journal of Immunology. 2007;179(2):1274-81.
54. Fernandes-Alnemri T, Wu J, Yu J, Datta P, Miller B, Jankowski W, et al. The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death & Differentiation. 2007;14(9):1590-604.
55. Vajjhala PR, Mirams RE, Hill JM. Multiple binding sites on the pyrin domain of ASC protein allow self-association and interaction with NLRP3 protein. Journal of Biological Chemistry. 2012;287(50):41732-43.
56. Lu A, Magupalli VG, Ruan J, Yin Q, Atianand MK, Vos MR, et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell. 2014;156(6):1193-206.
57. Xu H, Yang J, Gao W, Li L, Li P, Zhang L, et al. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature. 2014;513(7517):237-41.
58. Aubert DF, Xu H, Yang J, Shi X, Gao W, Li L, et al. A Burkholderia type VI effector deamidates Rho GTPases to activate the pyrin inflammasome and trigger inflammation. Cell host & microbe. 2016;19(5):664-74.
59. Richards N, Schaner P, Diaz A, Stuckey J, Shelden E, Wadhwa A, et al. Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis. Journal of Biological Chemistry. 2001;276(42):39320-9.
60. Park YH, Wood G, Kastner DL, Chae JJ. Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS. Nature immunology. 2016;17(8):914.
61. Keller M, Rüegg A, Werner S, Beer H-D. Active caspase-1 is a regulator of unconventional protein secretion. Cell. 2008;132(5):818-31.
62. Haznedaroglu S, Ozturk M, Sancak B, Goker B, Onat A, Bukan N, et al. Serum interleukin 17 and interleukin 18 levels in familial Mediterranean fever. Clinical and experimental rheumatology. 2005;23(4):S.
63. Köklü S, Öztürk MA, Balcı M, Yüksel O, Ertenli I, Kiraz S. Interferon-gamma levels in familial Mediterranean fever. Joint Bone Spine. 2005;72(1):38-40.
64. Ibrahim JN, Jeru I, Lecron J-C, Medlej-Hashim M. Cytokine signatures in hereditary fever syndromes (HFS). Cytokine & growth factor reviews. 2017;33:19-34.
65. Ben-Zvi I, Livneh A. Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nature Reviews Rheumatology. 2011;7(2):105-12.
66. Rozenbaum M, Katz R, Rozner I, Pollack S. Decreased interleukin 1 activity released from circulating monocytes of patients with familial Mediterranean fever during in vitro stimulation by lipopolysaccharide. The Journal of Rheumatology. 1992;19(3):416-8.
67. Bagci S, Toy B, Tuzun A, Ates Y, Aslan M, Inal A, et al. Continuity of cytokine activation in patients with familial Mediterranean fever. Clinical rheumatology. 2004;23(4):333-7.
68. Notarnicola C, Didelot M, Seguret F, Demaille J, Touitou I. Enhanced cytokine mRNA levels in attack-free patients with familial Mediterranean fever. Genes & Immunity. 2002;3(1):43-5.
69. Yalçınkaya F, Özen S, Özçakar ZB, Aktay N, Çakar N, Düzova A, et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology. 2009;48(4):395-8.
70. Padeh S, Berkun Y. Familial Mediterranean fever. Current Opinion in Rheumatology. 2016;28(5):523-9.
71. Padeh S, Livneh A, Pras E, Shinar Y, Lidar M, Feld O, et al. Familial Mediterranean Fever in the first two years of life: a unique phenotype of disease in evolution. The Journal of pediatrics. 2010;156(6):985-9.
72. Kees S, Langevitz P, Zemer D, Padeh S, Pras M, Linveh A. Attacks of pericarditis as a manifestation of familial Mediterranean fever (FMF). QJM: An International Journal of Medicine. 1997;90(10):643-7.
73. Eshel G, Vinograd I, Barr J, Zemer D. Acute scrotal pain complicating familial Mediterranean fever in children. Journal of British Surgery. 1994;81(6):894-6.
74. İnce E, Çakar N, Tekin M, Kendirli T, Özkaya N, Akar N, et al. Arthritis in children with familial Mediterranean fever. Rheumatology international. 2002;21(6):213-7.
75. Federici S, Sormani MP, Ozen S, Lachmann HJ, Amaryan G, Woo P, et al. Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers. Annals of the rheumatic diseases. 2015;74(5):799-805.
76. Garcia-Gonzalez A, Weisman MH, editors. The arthritis of familial Mediterranean fever. Seminars in arthritis and rheumatism; 1992: Elsevier.
77. Uthman I, Hajj-Ali RA, Arayssi T, Masri A-F, Nasr F. Arthritis in familial Mediterranean fever. Rheumatology international. 2001;20(4):145-8.
78. Eshed I, Rosman Y, Livneh A, Kedem R, Langevitz P, Ben‐Zvi I, et al. Exertional leg pain in familial Mediterranean fever: a manifestation of an underlying enthesopathy and a marker of more severe disease. Arthritis & Rheumatology. 2014;66(11):3221-6.
79. Langevitz P, Zemer D, Livneh A, Shemer J, Pras M. Protracted febrile myalgia in patients with familial Mediterranean fever. The Journal of rheumatology. 1994;21(9):1708-9.
80. Bayram MT, Çankaya T, Bora E, Kavukçu S, Ülgenalp A, Soylu A, et al. Risk factors for subclinical inflammation in children with Familial Mediterranean fever. Rheumatology international. 2015;35(8):1393-8.
81. Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. New England Journal of Medicine. 2003;349(6):583-96.
82. Kasifoglu T, Bilge SY, Sari I, Solmaz D, Senel S, Emmungil H, et al. Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study. Rheumatology. 2014;53(4):741-5.
83. Medlej-Hashim M, Delague V, Chouery E, Salem N, Rawashdeh M, Lefranc G, et al. Amyloidosis in familial Mediterranean fever patients: correlation with MEFV genotype and SAA1 and MICA polymorphisms effects. BMC medical genetics. 2004;5(1):1-6.
84. Kallinich T, Wittkowski H, Keitzer R, Roth J, Foell D. Neutrophil-derived S100A12 as novel biomarker of inflammation in familial Mediterranean fever. Annals of the rheumatic diseases. 2010;69(4):677-82.
85. Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, et al. Natural history and outcome in systemic AA amyloidosis. New England Journal of Medicine. 2007;356(23):2361-71.
86. Stojanovic KS, Hentgen V, Fellahi S, Georgin-Lavialle S, Amselem S, Grateau G, et al. Concordance between CRP and SAA in familial Mediterranean fever during attack-free period: a study of 218 patients. Clinical biochemistry. 2017;50(4-5):206-9.
87. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis & Rheumatism. 1997;40(10):1879-85.
88. Demirkaya E, Saglam C, Turker T, Koné-Paut I, Woo P, Doglio M, et al. Performance of different diagnostic criteria for familial Mediterranean fever in children with periodic fevers: results from a multicenter international registry. The Journal of rheumatology. 2016;43(1):154-60.
89. Sag E, Demirel D, Demir S, Atalay E, Akca U, Bilginer Y, et al., editors. Performance of the new ‘Eurofever/PRINTO classification criteria’in FMF patients. Seminars in arthritis and rheumatism; 2020: Elsevier.
90. Van Gijn ME, Ceccherini I, Shinar Y, Carbo EC, Slofstra M, Arostegui JI, et al. New workflow for classification of genetic variants’ pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). Journal of Medical Genetics. 2018;55(8):530-7.
91. Hentgen V, Grateau G, Stankovic‐Stojanovic K, Amselem S, Jéru I. Familial Mediterranean fever in heterozygotes: are we able to accurately diagnose the disease in very young children? Arthritis & Rheumatism. 2013;65(6):1654-62.
92. Nakayama M, Oda H, Nakagawa K, Yasumi T, Kawai T, Izawa K, et al. Accurate clinical genetic testing for autoinflammatory diseases using the next-generation sequencing platform MiSeq. Biochemistry and biophysics reports. 2017;9:146-52.
93. Karacan İ, Balamir A, Uğurlu S, Aydın AK, Everest E, Zor S, et al. Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study. Rheumatology international. 2019;39(5):911-9.
94. Ozen S, Bilginer Y. A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nature Reviews Rheumatology. 2014;10(3):135.
95. Angelidis C, Kotsialou Z, Kossyvakis C, Vrettou A-R, Zacharoulis A, Kolokathis F, et al. Colchicine pharmacokinetics and mechanism of action. Current pharmaceutical design. 2018;24(6):659-63.
96. Chappey ON, Niel E, Wautier JL, Hung PP, Dervichian M, Cattan D, et al. Colchicine disposition in human leukocytes after single and multiple oral administration. Clinical Pharmacology & Therapeutics. 1993;54(4):360-7.
97. Bhattacharyya B, Panda D, Gupta S, Banerjee M. Anti‐mitotic activity of colchicine and the structural basis for its interaction with tubulin. Medicinal research reviews. 2008;28(1):155-83.
98. Bismuth C, Gaultier M, Conso F. Medullary aplasia after acute colchicine poisoning. 20 cases. La Nouvelle presse medicale. 1977;6(19):1625-9.
99. Putterman C, Ben-Chetrit E, Caraco Y, Levy M, editors. Colchicine intoxication: clinical pharmacology, risk factors, features, and management. Seminars in arthritis and rheumatism; 1991: Elsevier.
100. Ozdemir R, Bayrakci B, Teksam O. Fatal poisoning in children: acute colchicine intoxication and new treatment approaches. Clinical toxicology. 2011;49(8):739-43.
101. Mor A, Shinar Y, Zaks N, Langevitz P, Chetrit A, Shtrasburg S, et al., editors. Evaluation of disease severity in familial Mediterranean fever. Seminars in arthritis and rheumatism; 2005: Elsevier.
102. Polat A, Acikel C, Sozeri B, Dursun I, Kasapcopur O, Gulez N, et al. Comparison of the efficacy of once-and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever–a randomized controlled noninferiority trial. Arthritis research & therapy. 2016;18(1):1-9.
103. Livneh A, Zemer D, Langevitz P, Laor A, Sohar E, Pras M. Colchicine treatment of AA amyloidosis of familial Mediterranean fever. Arthritis & Rheumatism. 1994;37(12):1804-11.
104. Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kélaïdi C, Blanche P. Acute colchicine intoxication during clarithromycin administration. Annals of Pharmacotherapy. 2004;38(12):2074-7.
105. Ozen S, Kone-Paut I, Gül A, editors. Colchicine resistance and intolerance in familial mediterranean fever: Definition, causes, and alternative treatments. Seminars in arthritis and rheumatism; 2017: Elsevier.
106. Özen S, Sag E, Ben-Chetrit E, Gattorno M, Gül A, Hashkes PJ, et al. Defining colchicine resistance/intolerance in patients with familial Mediterranean fever: a modified-Delphi consensus approach. Rheumatology. 2020.
107. Ozen S, Ben-Cherit E, Foeldvari I, Amarilyo G, Ozdogan H, Vanderschueren S, et al. Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial. Annals of the rheumatic diseases. 2020;79(10):1362-9.
108. Tufan A, Babaoglu MO, Akdogan A, Yasar U, Calguneri M, Kalyoncu U, et al. Association of drug transporter gene ABCB1 (MDR1) 3435C to T polymorphism with colchicine response in familial Mediterranean fever. The Journal of rheumatology. 2007;34(7):1540-4.
109. Ozer I, Mete T, Turkeli Sezer O, Kolbasi Ozgen G, Kucuk GO, Kaya C, et al. Association between colchicine resistance and vitamin D in familial Mediterranean fever. Renal failure. 2015;37(7):1122-5.
110. Köhler BM, Lorenz H-M, Blank N. IL1-blocking therapy in colchicine-resistant familial Mediterranean fever. European journal of rheumatology. 2018;5(4):230.
111. Sag E, Akal F, Atalay E, Akca UK, Demir S, Demirel D, et al. Anti-IL1 treatment in colchicine-resistant paediatric FMF patients: real life data from the HELIOS registry. Rheumatology. 2020;59(11):3324-9.
112. Ben‐Zvi I, Kukuy O, Giat E, Pras E, Feld O, Kivity S, et al. Anakinra for colchicine‐resistant familial Mediterranean fever: a randomized, double‐blind, placebo‐controlled trial. Arthritis & Rheumatology. 2017;69(4):854-62.
113. Kacar M, Savic S, van der Hilst JC. The efficacy, safety and tolerability of canakinumab in the treatment of familial Mediterranean fever: a systematic review of the literature. Journal of inflammation research. 2020;13:141.
114. Hashkes PJ, Spalding SJ, Hajj-Ali R, Giannini EH, Johnson A, Barron KS, et al. The effect of rilonacept versus placebo on health-related quality of life in patients with poorly controlled familial Mediterranean fever. BioMed research international. 2014;2014.
115. El Hasbani G, Jawad A, Uthman I. Update on the management of colchicine resistant Familial Mediterranean Fever (FMF). Orphanet journal of rare diseases. 2019;14(1):1-12.
116. Bilgen SA, Kilic L, Akdogan A, Kiraz S, Kalyoncu U, Karadag O, et al. Effects of Anti-Tumor Necrosis Factor Agents for Familial Mediterranean Fever Patients With Chronic Arthritis and/or Sacroiliitis Who Were Resistant to Colchicine Treatment. JCR: Journal of Clinical Rheumatology. 2011;17(7):358-62.
117. Sönmez HE, Batu ED, Özen S. Familial Mediterranean fever: current perspectives. Journal of inflammation research. 2016;9:13.
118. Yildiz M, Adrovic A, Tasdemir E, Baba-Zada K, Aydin M, Koker O, et al. Evaluation of co-existing diseases in children with familial Mediterranean fever. Rheumatology international. 2020;40(1):57-64.
119. Batu ED, Kara Eroğlu F, Tsoukas P, Hausmann JS, Bilginer Y, Kenna MA, et al. Periodic fever, aphthosis, pharyngitis, and adenitis syndrome: analysis of patients from two geographic areas. Arthritis care & research. 2016;68(12):1859-65.
120. Aydin F, Özçakar ZB, Çakar N, Çelikel E, Uncu N, Çelikel Acar B, et al. Sacroiliitis in Children With Familial Mediterranean Fever. JCR: Journal of Clinical Rheumatology. 2019;25(2):69-73.
121. Turan A, Mercan R, Bitik B, Kucuk H, Ozturk M, Tufan A. Magnetic resonance imaging features of Familial Mediterranean Fever associated spondyloarthritis. Pediatric Rheumatology. 2015;13(1):1-.
122. Sönmez HE, Batu ED, Demir S, Bilginer Y, Özen S. Comparison of patients with familial Mediterranean fever accompanied with sacroiliitis and patients with juvenile spondyloarthropathy. Clinical and experimental rheumatology. 2017;35(6):124-7.
123. Paç Kısaarslan A, Şahin N, Özdemir Çiçek S, Gündüz Z, Poyrazoğlu H, Düşünsel R. Evaluation of familial Mediterranean fever patients concomitant with juvenile spondyloarthropathy. Modern Rheumatology. 2021;31(3):718-24.
124. Li Z, Akar S, Yarkan H, Lee SK, Çetin P, Can G, et al. Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis. PLoS genetics. 2019;15(4):e1008038.
125. Feld O, Yahalom G, Livneh A. Neurologic and other systemic manifestations in FMF: published and own experience. Best Practice & Research Clinical Rheumatology. 2012;26(1):119-33.
126. Gandhi R, Laroni A, Weiner HL. Role of the innate immune system in the pathogenesis of multiple sclerosis. Journal of neuroimmunology. 2010;221(1-2):7-14.
127. Hemmer B, Kerschensteiner M, Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. The Lancet Neurology. 2015;14(4):406-19.
128. Huang W-X, Huang P, Hillert J. Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis. Multiple Sclerosis Journal. 2004;10(5):482-7.
129. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. The Journal of rheumatology. 2004;31(2):390-2.
130. Sepriano A, Ramiro S, van der Heijde D, van Gaalen F, Hoonhout P, Molto A, et al. What is axial spondyloarthritis? A latent class and transition analysis in the SPACE and DESIR cohorts. Annals of the rheumatic diseases. 2020;79(3):324-31.
131. Demirkaya E, Ozen S, Bilginer Y, Ayaz N, Makay B, Unsal E, et al. Paediatric rheumatology. Clinical and experimental rheumatology. 2011;29:111-6.
132. Yilmaz M, Kendirli SG, Altıntas DU, Karakoc GB, Inal A, Kılıc M. Juvenile idiopathic arthritis profile in Turkish children. Pediatrics International. 2008;50(2):154-8.
133. Sahin S, Acari C, Sonmez HE, Kilic FZ, Sag E, Dundar HA, et al. Frequency of juvenile idiopathic arthritis and associated uveitis in pediatric rheumatology clinics in Turkey: A retrospective study, JUPITER. Pediatric Rheumatology. 2021;19(1):1-10.
134. Saurenmann R, Rose J, Tyrrell P, Feldman B, Laxer R, Schneider R, et al. Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor. Arthritis & Rheumatism. 2007;56(6):1974-84.
135. Weiss PF, Beukelman T, Schanberg LE, Kimura Y, Colbert RA. Enthesitis-related arthritis is associated with higher pain intensity and poorer health status in comparison with other categories of juvenile idiopathic arthritis: the Childhood Arthritis and Rheumatology Research Alliance Registry. The Journal of rheumatology. 2012;39(12):2341-51.
136. Gomez K, Raza K, Jones S, Kennedy L, Calin A. Juvenile onset ankylosing spondylitis--more girls than we thought? The Journal of rheumatology. 1997;24(4):735-7.
137. Khan MA. An update on the genetic polymorphism of HLA-B* 27 with 213 alleles encompassing 160 subtypes (and still counting). Current rheumatology reports. 2017;19(2):9.
138. Kavadichanda CG, Geng J, Bulusu SN, Negi VS, Raghavan M. Spondyloarthritis and the Human Leukocyte Antigen (HLA)-B* 27 Connection. Frontiers in Immunology. 2021;12:497.
139. Sherlock JP, Joyce-Shaikh B, Turner SP, Chao C-C, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+ CD4− CD8− entheseal resident T cells. Nature medicine. 2012;18(7):1069-76.
140. DeLay ML, Turner MJ, Klenk EI, Smith JA, Sowders DP, Colbert RA. HLA–B27 misfolding and the unfolded protein response augment interleukin‐23 production and are associated with Th17 activation in transgenic rats. Arthritis & Rheumatism. 2009;60(9):2633-43.
141. Ito Y, Usui T, Kobayashi S, Iguchi‐Hashimoto M, Ito H, Yoshitomi H, et al. Gamma/delta T cells are the predominant source of interleukin‐17 in affected joints in collagen‐induced arthritis, but not in rheumatoid arthritis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 2009;60(8):2294-303.
142. Mielants H, Veys E, Goemaere S, Cuvelier C, De Vos M. A prospective study of patients with spondyloarthropathy with special reference to HLA-B27 and to gut histology. The Journal of rheumatology. 1993;20(8):1353-8.
143. Mielants H, Veys E, Cuvelier C, De Vos M, Goemaere S, De Clercq L, et al. The evolution of spondyloarthropathies in relation to gut histology. III. Relation between gut and joint. The Journal of rheumatology. 1995;22(12):2279-84.
144. Stoll ML, Kumar R, Morrow CD, Lefkowitz EJ, Cui X, Genin A, et al. Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis research & therapy. 2014;16(6):1-10.
145. Taurog JD, Richardson JA, Croft J, Simmons WA, Zhou M, Fernández-Sueiro JL, et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. Journal of Experimental Medicine. 1994;180(6):2359-64.
146. Clemente JC, Manasson J, Scher JU. The role of the gut microbiome in systemic inflammatory disease. Bmj. 2018;360.
147. Cortes A, Pulit SL, Leo PJ, Pointon JJ, Robinson PC, Weisman MH, et al. Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nature communications. 2015;6(1):1-8.
148. Lamot L, Borovecki F, Tambic Bukovac L, Vidovic M, Perica M, Gotovac K, et al. Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis. PloS one. 2014;9(12):e115416.
149. Cosan F, Üstek D, Oku B, Duymaz‐Tozkir J, Cakiris A, Abaci N, et al. Association of familial Mediterranean fever–related MEFV variations with ankylosing spondylitis. Arthritis & Rheumatism. 2010;62(11):3232-6.
150. Gülhan B, Akkuş A, Özçakar L, Beşbaş N, Özen S. Paediatric rheumatology; Are MEFV mutations susceptibility factors in enthesitis-related arthritis patients in the eastern Mediterranean. Clin Exp Rheumatol. 2014;32(suppl 84):s160-s4.
151. Bhattacharya S, Misra R, Aggarwal A. Patients with enthesitis related arthritis show similar monocyte function pattern as seen in adult axial spondyloarthropathy. Pediatric Rheumatology. 2020;18(1):1-11.
152. Gaur P, Myles A, Misra R, Aggarwal A. Intermediate monocytes are increased in enthesitis‐related arthritis, a category of juvenile idiopathic arthritis. Clinical & Experimental Immunology. 2017;187(2):234-41.
153. Gaur P, Misra R, Aggarwal A. Natural killer cell and gamma delta T cell alterations in enthesitis related arthritis category of juvenile idiopathic arthritis. Clinical immunology. 2015;161(2):163-9.
154. Saxena N, Aggarwal A, Misra R. Elevated concentrations of monocyte derived cytokines in synovial fluid of children with enthesitis related arthritis and polyarticular types of juvenile idiopathic arthritis. The Journal of rheumatology. 2005;32(7):1349-53.
155. Mahendra A, Misra R, Aggarwal A. Th1 and Th17 predominance in the enthesitis-related arthritis form of juvenile idiopathic arthritis. The Journal of rheumatology. 2009;36(8):1730-6.
156. Rahman MT, Myles A, Gaur P, Misra R, Aggarwal A. TLR4 endogenous ligand MRP8/14 level in enthesitis-related arthritis and its association with disease activity and TLR4 expression. Rheumatology. 2014;53(2):270-4.
157. Gupta L, Bhattacharya S, Agarwal V, Aggarwal A. Elevated levels of serum MRP8/14 in ankylosing spondylitis: associated with peripheral arthritis and active disease. Clinical rheumatology. 2016;35(12):3075-9.
158. Myles A, Tuteja A, Aggarwal A. Synovial fluid mononuclear cell gene expression profiling suggests dysregulation of innate immune genes in enthesitis-related arthritis patients. Rheumatology. 2012;51(10):1785-9.
159. Cánovas R, Cobb J, Brozynska M, Bowes J, Li YR, Smith SL, et al. Genomic risk scores for juvenile idiopathic arthritis and its subtypes. Annals of the rheumatic diseases. 2020;79(12):1572-9.
160. Weiss PF, Klink AJ, Behrens EM, Sherry DD, Finkel TH, Feudtner C, et al. Enthesitis in an inception cohort of enthesitis‐related arthritis. Arthritis care & research. 2011;63(9):1307-12.
161. Cabral DA, Malleson PN, Petty RE. Spondyloarthropathies of childhood. Pediatric Clinics of North America. 1995;42(5):1051-70.
162. Pagnini I, Savelli S, Matucci-Cerinic M, Fonda C, Cimaz R, Simonini G. Early predictors of juvenile sacroiliitis in enthesitis-related arthritis. The Journal of rheumatology. 2010;37(11):2395-401.
163. Fisher C, Ioannou Y, Hall-Craggs M, Sen D. Enthesitis related arthritis; a new era of understanding. Ann Paediatr Rheum. 2012;1(1):8-16.
164. Moll JM, Wright V. Normal range of spinal mobility. An objective clinical study. Annals of the rheumatic diseases. 1971;30(4):381.
165. Flatø B, Smerdel A, Johnston V, Lien G, Dale K, Vinje O, et al. The influence of patient characteristics, disease variables, and HLA alleles on the development of radiographically evident sacroiliitis in juvenile idiopathic arthritis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 2002;46(4):986-94.
166. Walscheid K, Glandorf K, Rothaus K, Niewerth M, Klotsche J, Minden K, et al. Enthesitis-related arthritis: prevalence and complications of associated uveitis in children and adolescents from a population-based nationwide study in Germany. The Journal of rheumatology. 2021;48(2):262-9.
167. Stoll ML, Punaro M, Patel AS. Fecal calprotectin in children with the enthesitis-related arthritis subtype of juvenile idiopathic arthritis. The Journal of rheumatology. 2011;38(10):2274-5.
168. Stoll ML, Patel AS, Punaro M, Dempsey-Robertson M. MR enterography to evaluate sub-clinical intestinal inflammation in children with spondyloarthritis. Pediatric Rheumatology. 2012;10(1):1-6.
169. Julkunen H. Synovial inflammatory cell reaction in chronic arthritis. Acta Rheumatologica Scandinavica. 1966;12(1-4):188-96.
170. Baeten D, Demetter P, Cuvelier C, Van den Bosch F, Kruithof E, Van Damme N, et al. Comparative study of the synovial histology in rheumatoid arthritis, spondyloarthropathy, and osteoarthritis: influence of disease duration and activity. Annals of the rheumatic diseases. 2000;59(12):945-53.
171. Aggarwal A, Misra DP. Enthesitis-related arthritis. Clinical rheumatology. 2015;34(11):1839-46.
172. Berntson L, Nordal E, Aalto K, Peltoniemi S, Herlin T, Zak M, et al. HLA-B27 predicts a more chronic disease course in an 8-year followup cohort of patients with juvenile idiopathic arthritis. The Journal of rheumatology. 2013;40(5):725-31.
173. Weiss PF, Chauvin NA, Klink AJ, Localio R, Feudtner C, Jaramillo D, et al. Detection of Enthesitis in Children With Enthesitis‐Related Arthritis: Dolorimetry Compared to Ultrasonography. Arthritis & Rheumatology. 2014;66(1):218-27.
174. Weber U, Maksymowych WP. Sensitivity and specificity of magnetic resonance imaging for axial spondyloarthritis. The American journal of the medical sciences. 2011;341(4):272-7.
175. Dreyfuss P, Dreyer SJ, Cole A, Mayo K. Sacroiliac joint pain. JAAOS-Journal of the American Academy of Orthopaedic Surgeons. 2004;12(4):255-65.
176. Ringold S, Angeles‐Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for non‐systemic polyarthritis, sacroiliitis, and enthesitis. Arthritis care & research. 2019;71(6):717-34.
177. Wanders A, Heijde Dvd, Landewé R, Béhier JM, Calin A, Olivieri I, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis & Rheumatism. 2005;52(6):1756-65.
178. Burgos-Vargas R, Vazquez-Mellado J, Pacheco-Tena C, Hernandez-Garduno A, Goycochea-Robles M. A 26 week randomised, double blind, placebo controlled exploratory study of sulfasalazine in juvenile onset spondyloarthropathies. Annals of the rheumatic diseases. 2002;61(10):941-2.
179. Van Rossum MA, van Soesbergen RM, Boers M, Zwinderman AH, Fiselier TJ, Franssen MJ, et al. Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment. Annals of the rheumatic diseases. 2007;66(11):1518-24.
180. Marino A, De Souza M, Giani T, Cimaz R. Pharmacotherapy for juvenile spondyloarthritis: an overview of the available therapies. Expert Opinion on Pharmacotherapy. 2020;21(17):2161-8.
181. André M. Patient education and foot disability in juvenile idiopathic arthritis: A physiotherapy perspective: Institutionen för klinisk neurovetenskap, arbetsterapi och …; 2005.
182. Tollisen A, Selvaag AM, Aulie HA, Lilleby V, Aasland A, Lerdal A, et al. Physical functioning, pain, and health‐related quality of life in adults with juvenile idiopathic arthritis: A longitudinal 30‐year followup study. Arthritis care & research. 2018;70(5):741-9.
183. Naveen R, Mohindra N, Jain N, Majumder S, Aggarwal A. Hip involvement in children with enthesitis related arthritis (ERA) is associated with poor outcomes in adulthood. Clinical rheumatology. 2021:1-9.
184. Minden K, Niewerth M, Listing J, Biedermann T, Bollow M, Schöntube M, et al. Long‐term outcome in patients with juvenile idiopathic arthritis. Arthritis & Rheumatism. 2002;46(9):2392-401.
185. Flatø B, Hoffmann‐Vold AM, Reiff A, Førre Ø, Lien G, Vinje O. Long‐term outcome and prognostic factors in enthesitis‐related arthritis: a case–control study. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 2006;54(11):3573-82.
186. Marino A, Weiss PF, Brandon TG, Lerman MA. Juvenile Spondyloarthritis: focus on uveitis. Pediatric Rheumatology. 2020;18(1):1-4.
187. Rypdal V, Arnstad ED, Aalto K, Berntson L, Ekelund M, Fasth A, et al. Predicting unfavorable long-term outcome in juvenile idiopathic arthritis: results from the Nordic cohort study. Arthritis research & therapy. 2018;20(1):1-10.
188. Gülhan B, Akkuş A, Özçakar L, Beşbaş N, Özen S. Paediatric rheumatology; Are MEFV mutations susceptibility factors in enthesitis-related arthritis patients in the eastern Mediterranean. Clin Exp Rheumatol. 2014;32(suppl 84):s160-4.
189. Aydin F, Özçakar ZB, Çakar N, Çelikel E, Uncu N, Acar BÇ, et al. Sacroiliitis in children with familial Mediterranean fever. JCR: Journal of Clinical Rheumatology. 2019;25(2):69-73.
190. Sharma D, Sharma BR, Vogel P, Kanneganti T-D. IL-1β and caspase-1 drive autoinflammatory disease independently of IL-1α or caspase-8 in a mouse model of familial Mediterranean fever. The American journal of pathology. 2017;187(2):236-44.
191. Ibrahim J-N, Jounblat R, Delwail A, Abou-Ghoch J, Salem N, Chouery E, et al. Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines. Cytokine. 2014;69(2):248-54.
192. Gang N, Drenth J, Langevitz P, Zemer D, Brezniak N, Pras M, et al. Activation of the cytokine network in familial Mediterranean fever. The Journal of rheumatology. 1999;26(4):890-7.
193. Simsek I, Pay S, Pekel A, Dinc A, Musabak U, Erdem H, et al. Serum proinflammatory cytokines directing T helper 1 polarization in patients with familial Mediterranean fever. Rheumatology international. 2007;27(9):807-11.
194. Zhu Q, Kanneganti T-D. Cutting edge: distinct regulatory mechanisms control proinflammatory cytokines IL-18 and IL-1β. The Journal of Immunology. 2017;198(11):4210-5.
195. Kim M, Chae J, Park Y, De Nardo D, Stirzaker R, Ko H, et al. Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1β. 2015.
196. Song M, Fang F, Dai X, Yu L, Fang M, Xu Y. MKL 1 is an epigenetic mediator of TNF‐α‐induced proinflammatory transcription in macrophages by interacting with ASH 2. FEBS letters. 2017;591(6):934-45.
197. Baykal Y, Saglam K, Yilmaz M, Taslipinar A, Akinci S, Inal A. Serum sIL-2r, IL-6, IL-10 and TNF-α level in familial Mediterranean fever patients. Clinical rheumatology. 2003;22(2):99-101.
198. Sharma D, Malik A, Guy C, Vogel P, Kanneganti T-D. TNF/TNFR axis promotes pyrin inflammasome activation and distinctly modulates pyrin inflammasomopathy. The Journal of clinical investigation. 2019;129(1):150-62.
199. Cambré I, Gaublomme D, Burssens A, Jacques P, Schryvers N, De Muynck A, et al. Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. Nature communications. 2018;9(1):1-14.
200. Otten MH, Prince FH, Twilt M, ARMBRUST W, HOPPENREIJS EP, KOOPMAN-KEEMINK Y, et al. Tumor necrosis factor-blocking agents for children with enthesitis-related arthritis—data from the Dutch arthritis and biologicals in children register, 1999–2010. The Journal of rheumatology. 2011;38(10):2258-63.
201. Koga T, Migita K, Sato S, Umeda M, Nonaka F, Kawashiri S-Y, et al. Multiple serum cytokine profiling to identify combinational diagnostic biomarkers in attacks of familial Mediterranean fever. Medicine. 2016;95(16).
202. Manukyan G, Ghazaryan K, Ktsoyan ZA, Tatyan M, Khachatryan Z, Hakobyan G, et al. Cytokine profile of Armenian patients with familial Mediterranean fever. Clinical biochemistry. 2008;41(10-11):920-2.
203. Bilginer Y, Roux-Lombard P, Dayer J M, Bakkaloglu A, Ozen S. Profile of cytokines, growth factors and chemokines during attacks of FMF. Pediatric Rheumatology. 2008;6(1):1-.
204. Özenci V, Kouwenhoven M, Huang Y, Kivisäkk P, Link H. Multiple sclerosis is associated with an imbalance between tumour necrosis factor-alpha (TNF-α)-and IL-10-secreting blood cells that is corrected by interferon-beta (IFN-β) treatment. Clinical & Experimental Immunology. 2000;120(1):147-53.
205. Shireman PK, Contreras‐Shannon V, Ochoa O, Karia BP, Michalek JE, McManus LM. MCP‐1 deficiency causes altered inflammation with impaired skeletal muscle regeneration. Journal of leukocyte biology. 2007;81(3):775-85.
206. Kholoussi S, Kholoussi N, El-Bassyouni HT, Morcos B, Abo-Shanab A. Serum levels of chemokines MCP-1, GRO-alpha and E-selectin correlates with familial Mediterranean fever. New Zealand Journal of Medical Laboratory Science. 2021;75(1):21-5.
207. Ozer HT, Erken E, Gunesacar R, Kara O. Serum RANTES, MIP-1α, and MCP-1 levels in Behçet’s disease. Rheumatology International. 2005;25(6):487-8.
208. Kavadichanda C, Shanoj K, Ganapathy S, Shah SI, Ananthakrishnan R, Sahoo J, et al. Factors associated with high cardiovascular risk in psoriatic arthritis and non-psoriatic spondyloarthritis. Rheumatology international. 2022:1-10.
