Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and disease activity in patients with rheumatoid arthritis in Iranian population

被引：27

作者：

Hashemi, Vida ^{[1
]}

Farrokhi, Amir Salek ^{[2
]}

Tanomand, Asghar ^{[1
]}

Babaloo, Zohreh ^{[3
]}

Hojjat-Farsangi, Mohammad ^{[4
,5
]}

Anvari, Enayat ^{[6
]}

Tahoori, Mohammad-Taher ^{[7
]}

Ezzeddini, Rana ^{[8
]}

Hosseini, Arezoo ^{[9
]}

Gharibi, Tohid ^{[9
]}

Ghalamfarsa, Ghasem ^{[10
]}

Jadidi-Niaragh, Farhad ^{[3
,9
,11
]}

机构：

[1] Maragheh Univ Med Sci, Dept Basic Sci, Fac Med, Maragheh, Iran

[2] Semnan Univ Med Sci, Sch Med, Dept Immunol, Semnan 3519899951, Iran

[3] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran

[4] Karolinska Univ Hosp Solna, CCK, Immune & Gene Therapy Lab, Dept Oncol Pathol, Stockholm, Sweden

[5] Karolinska Inst, Stockholm, Sweden

[6] Ilam Univ Med Sci, Dept Physiol, Fac Med, Ilam, Iran

[7] Shahid Sadoughi Univ Med Sci, Dept Immunol, Fac Med, Yazd, Iran

[8] Tarbiat Modares Univ, Dept Clin Biochem, Fac Med Sci, Tehran, Iran

[9] Tabriz Univ Med Sci, Dept Immunol, Fac Med, Tabriz, Iran

[10] Yasuj Univ Med Sci, Cellular & Mol Res Ctr, Yasuj, Iran

[11] Tabriz Univ Med Sci, Drug Appl Res Ctr, Tabriz, Iran

来源：

IMMUNOLOGY LETTERS | 2018年 / 204卷

关键词：

Rheumatoid arthritis; Foxp3; Polymorphism; Regulatory T cells; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUSCEPTIBILITY LOCUS; FOXP3/SCURFIN GENE; PERIPHERAL-BLOOD; ASSOCIATION; IMBALANCE; GRAVES; COMMON;

D O I：

10.1016/j.imlet.2018.10.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Rheumatoid arthritis (RA) is a chronic autoimmune disease that mainly affects joints and characterized by chronic joint inflammation and infiltration of various immune cells in the synovium. Forkhead box P3 (Foxp3)-expressing regulatory T cells (Tregs) play a crucial role in preventing autoimmunity and undesirable T cell responses. However, there are controversial reports regarding the defective function or frequency of these cells in various studies, which may be in part related to different polymorphisms of FoxP3 and influence of ethnicity on these differences. Therefore, the main subject of this study was to evaluate the association of Foxp3 gene polymorphism and Treg frequency in Iranian patients with RA. Accordingly, 240 RA patients diagnosed according to American college of rheumatology 2010 criteria and 240 normal subjects were recruited for this study. Genomic DNA was genotyped for -3279 C/A Foxp3 gene SNP using the PCR-RFLP. The frequency of Tregs and serum levels of interleukin (IL)-10, transforming growth factor (TGF)-beta, anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were determined by flow cytometry and ELISA methods, respectively. The results showed a significant association of Foxp3 - 3279 A allele with augmented risk of RA in Iranian patients compared to wild-type allele. While the frequencies of CA and AA genotypes were significantly higher in patients, RA patients with AA genotype had a significant lower frequency of Tregs compared to patients with CC and CA genotypes. Consistently, TGF-beta and IL-10 significantly diminished in patients with AA genotype compared to patients with CA and CC genotypes. Our findings indicated that the AA genotype of Foxp3 in RA patients is associated with downregulation of Tregs and susceptibility to RA in the Iranian population.

引用

页码：16 / 22

页数：7

共 39 条

[1] 2010 Rheumatoid Arthritis Classification Criteria An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative [J].

Aletaha, Daniel ;

Neogi, Tuhina ;

Silman, Alan J. ;

Funovits, Julia ;

Felson, David T. ;

Bingham, Clifton O., III ;

Birnbaum, Neal S. ;

Burmester, Gerd R. ;

Bykerk, Vivian P. ;

Cohen, Marc D. ;

Combe, Bernard ;

Costenbader, Karen H. ;

Dougados, Maxime ;

Emery, Paul ;

Ferraccioli, Gianfranco ;

Hazes, Johanna M. W. ;

Hobbs, Kathryn ;

Huizinga, Tom W. J. ;

Kavanaugh, Arthur ;

Kay, Jonathan ;

Kvien, Tore K. ;

Laing, Timothy ;

Mease, Philip ;

Menard, Henri A. ;

Moreland, Larry W. ;

Naden, Raymond L. ;

Pincus, Theodore ;

Smolen, Josef S. ;

Stanislawska-Biernat, Ewa ;

Symmons, Deborah ;

Tak, Paul P. ;

Upchurch, Katherine S. ;

Vencovsky, Jiri ;

Wolfe, Frederick ;

Hawker, Gillian .

ARTHRITIS AND RHEUMATISM, 2010, 62 (09) :2569-2581

[2]

Alunno A., 2015, MEDIATORS INFLAMM, V2015

[3] Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation [J].

Asano, M ;

Toda, M ;

Sakaguchi, N ;

Sakaguchi, S .

JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (02) :387-396

[4] Identification, Isolation, and Functional Assay of Regulatory T Cells [J].

Azimi, Maryam ;

Aslani, Saeed ;

Mortezagholi, Sahar ;

Salek, Amir ;

Javan, Mohammad Reza ;

Rezaiemanesh, Alireza ;

Ghaedi, Mojgan ;

Gholamzad, Mehrdad ;

Salehi, Eisa .

IMMUNOLOGICAL INVESTIGATIONS, 2016, 45 (07) :584-602

[5] A genome screen for linkage in Australian sibling-pairs with multiple sclerosis [J].

Ban, M ;

Stewart, GJ ;

Bennetts, BH ;

Heard, R ;

Simmons, R ;

Maranian, M ;

Compston, A ;

Sawcer, SJ .

GENES AND IMMUNITY, 2002, 3 (08) :464-469

[6] Genetic Susceptibility to Rheumatoid Arthritis: An Emerging Picture [J].

Barton, Anne ;

Worthington, Jane .

ARTHRITIS CARE & RESEARCH, 2009, 61 (10) :1441-1446

[7] A functional polymorphism in the promoter/enhancer region of the FOXP3/Scurfin gene associated with type 1 diabetes [J].

Bassuny, WM ;

Ihara, K ;

Sasaki, Y ;

Kuromaru, R ;

Kohno, H ;

Matsuura, N ;

Hara, T .

IMMUNOGENETICS, 2003, 55 (03) :149-156

[8] Common and different genetic background for rheumatoid arthritis and coeliac disease [J].

Coenen, Marieke J. H. ;

Trynka, Gosia ;

Heskamp, Sandra ;

Franke, Barbara ;

van Diemen, Cleo C. ;

Smolonska, Joanna ;

van Leeuwen, Miek ;

Brouwer, Elisabeth ;

Boezen, Marike H. ;

Postma, Dirkje S. ;

Platteel, Mathieu ;

Zanen, Pieter ;

Lammers, Jan-Willem W. J. ;

Groen, Harry J. M. ;

Mali, Willem P. T. M. ;

Mulder, Chris J. ;

Tack, Greetje J. ;

Verbeek, Wieke H. M. ;

Wolters, Victorien M. ;

Houwen, Roderick H. J. ;

Mearin, M. Luisa ;

van Heel, David A. ;

Radstake, Timothy R. D. J. ;

van Riel, Piet L. C. M. ;

Wijmenga, Cisca ;

Barrera, Pilar ;

Zhernakova, Alexandra .

HUMAN MOLECULAR GENETICS, 2009, 18 (21) :4195-4203

[9] New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study [J].

Cornelis, F ;

Faure, S ;

Martinez, M ;

Prud'Homme, JF ;

Fritz, P ;

Dib, C ;

Alves, H ;

Barrera, P ;

De Vries, N ;

Balsa, A ;

Pascual-Salcedo, D ;

Maenaut, K ;

Westhovens, R ;

Migliorini, P ;

Tran, TH ;

Delaye, A ;

Prince, N ;

Lefevre, C ;

Thomas, G ;

Poirier, M ;

Soubigou, S ;

Alibert, O ;

Lasbleiz, S ;

Fouix, S ;

Bouchier, C ;

Lioté, F ;

Loste, MN ;

Lepage, V ;

Charron, D ;

Gyapay, G ;

Lopes-Vaz, A ;

Kuntz, D ;

Bardin, T ;

Weissenbach, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (18) :10746-10750

[10] Imbalance of regulatory T cells in human autoimmune diseases [J].

Dejaco, C ;

Duftner, C ;

Grubeck-Loebenstein, B ;

Schirmer, M .

IMMUNOLOGY, 2006, 117 (03) :289-300

← 1 2 3 4 →