Adaptive ımmune system evaluation in familial mediterranean fever: clinical and ımmunological analysis
Main Article Content
Keywords
adaptive immune system, familial mediterranean fever (FMF), innate immune system, lymphocyte subset evaluation
Abstract
Background: Familial Mediterranean Fever is a common genetic autoinflammatory disease prevalent in the Mediterranean region. The clinical course of the disease is characterized by fever and serositis attacks. While defects in the innate immune system are known to play a role in the pathogenesis of the disease, the impact of the adaptive immune system remains unclear. Therefore, the main objective of this study is to analyze the adaptive immune system cells in FMF patients and investigate their relationship with the disease.
Methods: Our study includes 88 FMF patients with confirmed MEFV gene mutations. The demographic characteristics, clinical symptoms, genetic profiles, treatment methods, and any accompanying diseases of the patients were thoroughly examined. Additionally, lymphocyte subpopulations were analyzed using flow cytometry, and inflammatory markers and immunoglobulin levels were evaluated.
Results: Significant differences were observed in the distribution of adaptive immune system cells in FMF patients compared to the healthy reference group. In the analysis of lymphocyte subgroups, levels of CD3, CD4, CD19, CD16+56+, CD3CD4CD45RACD31, CD4+CD45RA+, CD8+CD45RA+, CD19+CD27+IgD+IgM+, CD19+CD27+IgD-IgM-, and CD19+CD38+CD21 were found to be lower compared to healthy individuals. Additionally, CD8, CD19+CD27-IgD+, and CD3/CD8/TCRGD cells were found to be higher. Moreover, in FMF patients with accompanying diseases, CD3, CD4, and CD19 values were statistically lower (p<0.001).
Conclusion: This study reveals that adaptive immune system cells are affected in FMF patients, suggesting their significant role in the disease’s pathophysiology. Immunological evaluations should be prioritized in the management of FMF, enabling personalized treatment plans for more effective outcomes.
References
2 Manukyan G, Aminov R. Update on pyrin functions and mechanisms of familial mediterranean fever. Front Microbiol. 2016;7:456. 10.3389/fmicb.2016.00456
3 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):1372–1380. 10.1093/rheumatology/kez410. PMid: 31598713
4 Tezcan ME, Acer Kasman S, Şen N, Osken S, Yılmaz-Oner S. Importance of hematological markers in familial Mediterranean fever in terms of disease severity and amyloidosis. Rheumatol Int. 2023;43(7):1313–1321. 10.1007/s00296-023-05290-w
5 Bayram RO, Özdemir H, Emsen A, Türk Dağı H, Artaç H. Reference ranges for serum immunoglobulin (IgG, IgA, and IgM) and IgG subclass levels in healthy children. Turk J Med Sci. 2019;49(2):497–505. 10.3906/sag-1807-282
6 Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther. 2021;6(1):128. 10.1038/s41392-021-00507-5
7 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. Rheumatol Int. 2020;40(1):57–64. 10.1007/s00296-019-04391-9
8 Lancieri M, Bustaffa M, Palmeri S, Prigione I, Penco F, Papa R, et al. An Update on Familial Mediterranean Fever. Int J Mol Sci. 2023;24(11):9584. 10.3390/ijms24119584
9 Schön MP. Adaptive and Innate Immunity in Psoriasis and Other Inflammatory Disorders. Front Immunol. 2019;10:1764. 10.3389/fimmu.2019.01764
10 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? Clin Exp Immunol. 2004;138(3):526–33. 10.1111/j.1365-2249.2004.02632.x
11 Dong C. Cytokine regulation and function in T cells. Annu Rev Immunol. 2021;39:51–76. 10.1146/annurev-immunol-061020-053702
12 Van den Broek T, Borghans JAM, van Wijk F. The full spectrum of human naive T cells. Nat Rev Immunol. 2018;18(6):363–373. 10.1038/s41577-018-0001-y
13 Oparaugo NC, Ouyang K, Nguyen NPN, Nelson AM, Agak GW. Human regulatory T cells: understanding the role of Tregs in select autoimmune skin diseases and post-transplant nonmelanoma skin cancers. Int J Mol Sci. 2023;24(2):1527. 10.3390/ijms24021527
14 Rimar D, Rosner I, Slobodin G, et al. The role of regulatory T cells in familial Mediterranean fever (FMF). Clin Rheumatol. 2012;31(5):885–888. 10.1007/s10067-011-1935-7
15 Al B, Bruno M, Röring RJ, Moorlag SJCFM, Suen TK, Klück V, et al. Peripheral T cell populations are differentially affected in familial mediterranean fever, chronic granulomatous disease, and gout. J Clin Immunol. 2023;43(8):2033–2048. 10.1007/s10875-023-01576-7
16 Ovadia A, Livneh A, Feld O, Ben-Zvi I, Kukuy E, Kivity S, et al. T helper 17 polarization in familial Mediterranean fever. Genes Immun. 2013;14(4):212–216. 10.1038/gene.2013.6
17 Kholoussi S, Kholoussi N, Zaki ME, El-Bassyouni HT, Elnady H, Morcos B, et al. Immunological Evaluation in Patients with Familial Mediterranean fever. Maced J Med Sci. 2018;6(2):310–313. 10.3889/oamjms.2018.079
18 Ilfeld D, Feierman E, Kuperman O, Kivity S, Topilsky M, Netzer L, et al. Effect of colchicine on T cell subsets of healthy volunteers. Immunology. 1984;53(3):595–598.
19 Notarnicola C, Didelot MN, Seguret F, Demaille J, Touitou I. Enhanced cytokine mRNA levels in attack-free patients with familial Mediterranean fever. Genes Immun. 2002;3(1):43–45. 10.1038/sj.gene.6363813
