Stable GAD65 autoantibody epitope patterns in type 1 diabetes children five years after onset

被引:13
作者
Hampe, CS
Hammerle, LP
Bekris, L
Örtqvist, E
Persson, B
Lernmark, Å
机构
[1] Univ Washington, Dept Med, Robert H Willams Lab, Seattle, WA 98195 USA
[2] Karolinska Inst, Dept Women & Child Hlth, Stockholm, Sweden
关键词
autoimmunity; epitopes; type; 1; diabetes; GAD65; GAD67;
D O I
10.1006/jaut.2001.0564
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Autoantibodies to GAD65 (GAD65Ab) are prominent in type 1 diabetes. These autoantibodies may be present both years before and after the clinical diagnosis of type 1 diabetes and are widely used as a marker for the disease. Recently it has been demonstrated that progression to type I diabetes is accompanied by GAD65Ab epitope maturation. Here we examine whether autoantibody maturation processes also progress after the clinical diagnosis of type I diabetes. A-ntibody reactivity to GAD65, GAD67 and GAD65/67 fusion proteins was measured by radioimmunoassays in 62 children with type 1 diabetes. Samples were taken at diagnosis and five years later. While the overall GAD65Ab level declined over time, the epitope pattern was remarkably stable with no significant changes in binding pattern. Loss of GAD65Ab-positivity was associated with significantly lower GAD65Ab indices at diagnosis compared to patients' sera that remained GAD65Ab-positive. The decrease in GAD63Ab levels did not correlate to residual C-peptide levels. Our data suggest that processes controlling GAD65Ab levels and epitope binding patterns remain stable during the first five years of type 1 diabetes. (C) 2002 Elsevier Science Ltd.
引用
收藏
页码:49 / 53
页数:5
相关论文
共 30 条
[1]   64000 MR AUTOANTIBODIES AS PREDICTORS OF INSULIN-DEPENDENT DIABETES [J].
ATKINSON, MA ;
MACLAREN, NK ;
SCHARP, DW ;
LACY, PE ;
RILEY, WJ .
LANCET, 1990, 335 (8702) :1357-1360
[2]   IDENTIFICATION OF THE 64K AUTOANTIGEN IN INSULIN-DEPENDENT DIABETES AS THE GABA-SYNTHESIZING ENZYME GLUTAMIC-ACID DECARBOXYLASE [J].
BAEKKESKOV, S ;
AANSTOOT, HJ ;
CHRISTGAU, S ;
REETZ, A ;
SOLIMENA, M ;
CASCALHO, M ;
FOLLI, F ;
RICHTEROLESEN, H ;
CAMILLI, PD .
NATURE, 1990, 347 (6289) :151-156
[3]   Maturation of the humoral autoimmune response to epitopes of GAD in preclinical childhood type 1 diabetes [J].
Bonifacio, E ;
Lampasona, V ;
Bernasconi, L ;
Ziegler, AG .
DIABETES, 2000, 49 (02) :202-208
[4]   PERSISTENCE OF SERUM ANTIBODIES TO 64,000-MR ISLET CELL PROTEIN AFTER ONSET OF TYPE-I DIABETES [J].
CHRISTIE, MR ;
DANEMAN, D ;
CHAMPAGNE, P ;
DELOVITCH, TL .
DIABETES, 1990, 39 (06) :653-656
[5]   2 DISTINCT GLUTAMIC-ACID DECARBOXYLASE AUTOANTIBODY SPECIFICITIES IN IDDM TARGET DIFFERENT EPITOPES [J].
DAW, K ;
POWERS, AC .
DIABETES, 1995, 44 (02) :216-220
[6]   RADIOIMMUNOASSAYS FOR GLUTAMIC-ACID DECARBOXYLASE (GAD65) AND GAD65 AUTOANTIBODIES USING S-35 OR H-3 RECOMBINANT HUMAN LIGANDS [J].
FALORNI, A ;
ORTQVIST, E ;
PERSSON, B ;
LERNMARK, A .
JOURNAL OF IMMUNOLOGICAL METHODS, 1995, 186 (01) :89-99
[7]  
Falorni A, 1996, DIABETOLOGIA, V39, P1091
[8]  
GRUBIN CE, 1994, DIABETOLOGIA, V37, P344, DOI 10.1007/BF00408469
[9]   GLUTAMATE DECARBOXYLASE-ANTIBODIES, INSULIN-ANTIBODIES AND ISLET-CELL-ANTIBODIES AND HLA TYPING TO DETECT DIABETES IN A GENERAL POPULATION-BASED STUDY OF SWEDISH CHILDREN [J].
HAGOPIAN, WA ;
SANJEEVI, CB ;
KOCKUM, I ;
LANDINOLSSON, M ;
KARLSEN, AE ;
SUNDKVIST, G ;
DAHLQUIST, G ;
PALMER, J ;
LERNMARK, A .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (04) :1505-1511
[10]   Species-specific autoantibodies in type 1 diabetes [J].
Hampe, CS ;
Örtqvist, E ;
Rolandsson, O ;
Landin-Olsson, M ;
Törn, C ;
Ågren, Å ;
Persson, B ;
Schranz, DB ;
Lernmark, Å .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (02) :643-648