Pendrin Is a Novel Autoantigen Recognized by Patients with Autoimmune Thyroid Diseases

被引:24
作者
Yoshida, Akio [1 ]
Hisatome, Ichiro [1 ]
Taniguchi, Shinichi [2 ]
Shirayoshi, Yasuaki [1 ]
Yamamoto, Yasutaka [1 ]
Miake, Junichiro [1 ]
Ohkura, Tsuyoshi [2 ]
Akama, Takeshi [3 ]
Igawa, Osamu [2 ]
Shigemasa, Chiaki [2 ]
Kamijo, Keiichi [4 ]
Ikuyama, Shoichiro [5 ]
Caturegli, Patrizio [6 ]
Suzuki, Koichi
机构
[1] Tottori Univ, Grad Sch Med, Dept Genet & Regenerat Med, Div Regenerat Med & Therapeut, Tottori 6838504, Japan
[2] Tottori Univ, Fac Med, Dept Internal Med 1, Tottori 6838504, Japan
[3] Natl Inst Infect Dis, Dept Bioregulat, Tokyo 1890002, Japan
[4] Kamijo Thyroid Res Inst, Sapporo, Hokkaido 0640822, Japan
[5] Kyushu Univ, Med Inst Bioregulat, Div Clin Immunol, Beppu, Oita 8740838, Japan
[6] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA
关键词
SODIUM-IODIDE SYMPORTER; NA+/I-SYMPORTER; SYNDROME GENE; GRAVES-DISEASE; APICAL PORTER; CELLS; SERA; PDS; TRANSPORTER; EXPRESSION;
D O I
10.1210/jc.2008-1732
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Pendrin is an apical protein of thyroid follicular cells, responsible for the efflux of iodide into the follicular lumen via an iodide-chloride transport mechanism. It is unknown whether pendrin is recognized by autoantibodies. Objective: Our objective was to examine the prevalence of pendrin antibodies in autoimmune thyroid diseases and compare with that of thyroglobulin, thyroperoxidase, TSH receptor, and sodium iodide symporter antibodies. Design: In a prevalent case-control study, we analyzed the sera of 140 autoimmune thyroid disease cases (100 with Graves' disease and 40 with Hashimoto's thyroiditis) and 80 controls (50 healthy subjects, 10 patients with papillary thyroid cancer, 10 with systemic lupus erythematosus, and 10 with rheumatoid arthritis). Pendrin antibodies were measured by immunoblotting using extract of COS-7 cells transfected with pendrin and a rabbit polyclonal pendrin antibody. Results: Pendrin antibodies were found in 81% of the cases and 9% of controls (odds ratio = 44; P < 0.0001). Among cases, pendrin antibodies were more frequent and of higher titers in Hashimoto's thyroiditis than in Graves' disease. Pendrin antibodies correlated significantly with thyroglobulin, thyroperoxidase, and sodium iodide symporter antibodies but not with TSH receptor antibodies. Pendrin antibodies were equally effective as thyroglobulin and thyroperoxidase antibodies in diagnosis of autoimmune thyroid diseases, especially Hashimoto's thyroiditis. Conclusions: The study identifies pendrin as a novel autoantigen recognized by patients with autoimmune thyroid diseases and proposes the use of pendrin antibodies as an accurate diagnostic tool. (J Clin Endocrinol Metab 94: 442-448, 2009)
引用
收藏
页码:442 / 448
页数:7
相关论文
共 29 条
[1]   The modulation of the human sodium iodide symporter activity by Graves' disease sera [J].
Ajjan, RA ;
Findlay, C ;
Metcalfe, RA ;
Watson, PF ;
Crisp, M ;
Ludgate, M ;
Weetman, AP .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (04) :1217-1221
[2]   Influence of a dominant cryptic epitope on autoimmune T cell tolerance [J].
Anderton, SM ;
Viner, NJ ;
Matharu, P ;
Lowrey, PA ;
Wraith, DC .
NATURE IMMUNOLOGY, 2002, 3 (02) :175-181
[3]   Expression of Na+/I- symporter and pendred syndrome genes in trophoblast cells [J].
Bidart, JM ;
Lacroix, L ;
Evain-Brion, D ;
Caillou, B ;
Lazar, V ;
Frydman, R ;
Bellet, D ;
Filetti, S ;
Schlumberger, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (11) :4367-4372
[4]   Rarity of anti- Na+/I- symporter (NIS) antibody with iodide uptake inhibiting activity in autoimmune thyroid diseases (AITD). [J].
Chin, HS ;
Chin, DKH ;
Morgenthaler, NG ;
Vassart, G ;
Costagliola, S .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (10) :3937-3940
[5]   Autoantibody against Na+/I- symporter in the sera of patients with autoimmune thyroid disease [J].
Endo, T ;
Kogai, T ;
Nakazato, M ;
Saito, T ;
Kaneshige, M ;
Onaya, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 224 (01) :92-95
[6]   Autoantibody against thyroid iodide transporter in the sera from patients with Hashimoto's thyroiditis possesses iodide transport inhibitory activity [J].
Endo, T ;
Kaneshige, N ;
Nakazato, M ;
Kogai, T ;
Saito, T ;
Onaya, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 228 (01) :199-202
[7]   Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS) [J].
Everett, LA ;
Glaser, B ;
Beck, JC ;
Idol, JR ;
Buchs, A ;
Heyman, M ;
Adawi, F ;
Hazani, E ;
Nassir, E ;
Baxevanis, AD ;
Sheffield, VC ;
Green, ED .
NATURE GENETICS, 1997, 17 (04) :411-422
[8]   A family of mammalian anion transporters and their involvement in human genetic diseases [J].
Everett, LA ;
Green, ED .
HUMAN MOLECULAR GENETICS, 1999, 8 (10) :1883-1891
[9]   Functional characterization of pendrin in a polarized cell system - Evidence for pendrin-mediated apical iodide efflux [J].
Gillam, MP ;
Sidhaye, AR ;
Lee, EJ ;
Rutishauser, J ;
Stephan, CW ;
Kopp, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (13) :13004-13010
[10]   Epidemiology and estimated population burden of selected autoimmune diseases in the United States [J].
Jacobson, DL ;
Gange, SJ ;
Rose, NR ;
Graham, NMH .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1997, 84 (03) :223-243