Serological reactivity of recombinant 1D autoantigen and its expression in human thyroid and eye muscle tissue: A possible autoantigenic link in Graves' patients

被引:13
作者
Kromminga, A
Hagel, C
Arndt, R
Schuppert, F
机构
[1] Inst Immunol Pathol & Mol Biol, D-22339 Hamburg, Germany
[2] Hannover Med Sch, Dept Clin Endocrionl, D-30173 Hannover, Germany
关键词
D O I
10.1210/jc.83.8.2817
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thyroid-associated ophthalmopathy (TAO) is a potentially severe autoimmune disease, in and around the orbit, usually accompanied by Graves' disease. It was the goal of this study to develop a serological indicator for TAO and to characterize its expression in human thyroid and eye muscle tissue. Thus, we have recloned the full-length 1D-complementary DNA and assessed its expression levels in 90 healthy and diseased human thyroids. Only Graves' patients suffering from TAO (n = 29) displayed a significant, 2.1-fold increase of 1D expression levels (P = 0.029), compared with normal controls (n = 9), as assessed using the Mann-Whitney U-test for paired, nonnormally distributed samples. In contrast, a decrease of 1D expression (to 40% of control normal values) was confined to thyroid autonomy (n = 19, P = 0.032). In all other diseased human thyroids, including Graves' thyroids from patients not suffering from clinically overt TAO (n = 9), 1D expression levels were not different from the healthy controls. 1D gene expression was demonstrated in both healthy (n = 10) and diseased (n = 10) eye muscle tissues. Furthermore, a recombinant protein derived from baculovirus-infected Sf9 insect cells was purified under both nondenaturing and denaturing conditions. While under nondenaturing conditions, the molecular mass of recombinant 1D was determined to be 85 kDa; denaturing isolation yielded the expected 64-kDa protein. Autoantibodies against denatured 1D protein were not detectable in sera of diseased or healthy subjects. Immunoreactivity against the 85-kDa, nondenatured protein, evaluated in a panel of 222 different human sera, showed that 82% of Graves' patients suffering from TAO had autoantibodies against recombinant 1D, whereas only 5% of the healthy controls were positive for antibodies against 1D. Taken together, our results demonstrate a high disease sensitivity and specificity of recombinant, nondenatured 1D, to distinguish Graves' disease with or without TAO from other forms of thyroid and/or eye disease. Prospective studies will have to show whether autoantibodies against 1D can also be used as a prognosticator of TAO.
引用
收藏
页码:2817 / 2823
页数:7
相关论文
共 26 条
[11]   INSITU HYBRIDIZATION OF THE MESSENGER-RNA FOR INTERFERON-GAMMA, INTERFERON-ALPHA-E, INTERFERON-BETA, INTERLEUKIN-1-BETA AND INTERLEUKIN-6 AND CHARACTERIZATION OF INFILTRATING CELLS IN THYROID TISSUES [J].
RUTENFRANZ, I ;
KRUSE, A ;
RINK, L ;
WENZEL, B ;
ARNHOLDT, H ;
KIRCHNER, H .
JOURNAL OF IMMUNOLOGICAL METHODS, 1992, 148 (1-2) :233-242
[12]  
Sambrook J., 2002, MOL CLONING LAB MANU
[13]   DETERMINATION OF NUCLEOTIDE-SEQUENCES IN DNA [J].
SANGER, F .
SCIENCE, 1981, 214 (4526) :1205-1210
[14]  
SCHATZ H, 1989, AKT ENDOKR STOFFW, V10, P146
[15]   Iodide, cytokines and TSH-receptor expression in Graves' disease [J].
Schuppert, F ;
Hiller, W ;
Weinland, G ;
HoangVu, C ;
vonzurMuhlen, A ;
Kohn, LD .
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 1996, 104 :68-74
[16]   THYROTROPIN RECEPTOR AND LEUKOCYTE ADHESION MOLECULES IN AUTOIMMUNE THYROID-DISEASE - A STUDY OF THEIR GENE-EXPRESSION BY NORTHERN BLOT ANALYSIS AND IN-SITU HYBRIDIZATION [J].
SCHUPPERT, F ;
REISER, M ;
HELDIN, NE ;
EDE, S ;
SCHEUMANN, GFW ;
DRALLE, H ;
VONZURMUHLEN, A .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 1994, 131 (05) :480-488
[17]   In vivo and in vitro evidence for iodide regulation of major histocompatibility complex class I and class II expression in Graves' disease [J].
Schuppert, F ;
Taniguchi, S ;
Schroder, S .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (10) :3622-3628
[18]   EXPRESSION LEVELS OF THE THYROTROPIN RECEPTOR GENE IN AUTOIMMUNE THYROID-DISEASE - COREGULATION WITH PARAMETERS OF THYROID-FUNCTION AND INVERSE RELATION TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASSE-I AND CLASSE-II [J].
SCHUPPERT, F ;
REISER, M ;
SCHEUMANN, GFW ;
HELDIN, NE ;
PRINGAKERBLOM, P ;
EDE, S ;
HAVERKAMP, G ;
DRALLE, H ;
VONZURMUHLEN, A .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1993, 76 (05) :1349-1356
[19]  
SZOSTECKI C, 1967, MAYO CLIN P, V42, P812
[20]   SPECTRUM OF THYROID DISEASE IN A COMMUNITY - WHICKHAM SURVEY [J].
TUNBRIDGE, WMG ;
EVERED, DC ;
HALL, R ;
APPLETON, D ;
BREWIS, M ;
CLARK, F ;
EVANS, JG ;
YOUNG, E ;
BIRD, T ;
SMITH, PA .
CLINICAL ENDOCRINOLOGY, 1977, 7 (06) :481-493