Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes
Aims/hypothesis. The aim of this study was to analyse the conformational and linear epitope profiles of glutamic acid decarboxylase antibody (GAD65-ab)-positive sera to find disease-specific epitope profiles and to study, whether GAD65-ab epitope recognition changes or spreads during the prediabetic...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2000
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| In: |
Diabetologia
Year: 2000, Jahrgang: 43, Heft: 2, Pages: 210-217 |
| ISSN: | 1432-0428 |
| DOI: | 10.1007/s001250050031 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s001250050031
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| Verfasserangaben: | P. Söhnlein, M. Müller, K. Syren, U. Hartmann, B.O. Böhm, H.M. Meinck, M. Knip, H.K. Akerblom, The Childhood Diabetes in Finland Study Group, W. Richter |
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| 245 | 1 | 0 | |a Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes |c P. Söhnlein, M. Müller, K. Syren, U. Hartmann, B.O. Böhm, H.M. Meinck, M. Knip, H.K. Akerblom, The Childhood Diabetes in Finland Study Group, W. Richter |
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| 520 | |a Aims/hypothesis. The aim of this study was to analyse the conformational and linear epitope profiles of glutamic acid decarboxylase antibody (GAD65-ab)-positive sera to find disease-specific epitope profiles and to study, whether GAD65-ab epitope recognition changes or spreads during the prediabetic period and, thus, can provide markers to differentiate early from later stages of progression to diabetes.¶Methods. Sera from subjects before (n = 21), at onset (n = 44), or at increased risk of Type I (insulin-dependent) diabetes mellitus (n = 20) and from patients with stiff-man syndrome (SMS, n = 18) or polyendocrine autoimmune syndrome (PAS, n = 21) were analysed for conformational and linear GAD65 epitope recognition by an immunohistochemical blocking test based on human monoclonal GAD65-ab (MICA 1-10) and western blotting of a GAD65 epitope-cDNA-library.¶Results. A redundant reactivity of many GAD65-ab positive sera to three major conformational (EP-1, EP-2, EP-3) and two dominant linear epitope clusters (amino acid 1-124 and 535-585) was observed in diabetes, polyendocrine autoimmune syndrome and stiff-man syndrome and no disease-specific epitopes or epitope-profiles were detected. Epitope recognition broadened with higher titres and with the vulnerability of patients to acquire additional autoimmune diseases apart from diabetes. Low GAD65-ab serum titres ( < 1200 arbitrary units) and EP-1 recognition in the absence of EP-2 binding characterised the early immune response. Changing epitope profiles combined stable recognition of EP-1 with gain or loss of reactivity to C-terminal epitopes during follow-up.¶Conclusion/interpretation. A maturing autoantibody response, which could spread from EP-1-recognition to other regions of GAD65, resulted in titre-related rather than disease-specific epitope profiles which were not sufficient to predict whether GAD65-ab positive subjects will progress to Type I diabetes, autoimmune polyendocrine syndrome or stiff-man syndrome. | ||
| 700 | 1 | |a Müller, M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Syren, K. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hartmann, U. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Böhm, B. O. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Meinck, Hans-Michael |e VerfasserIn |0 (DE-588)1048652114 |0 (DE-627)780862325 |0 (DE-576)402924983 |4 aut | |
| 700 | 1 | |a Knip, M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Akerblom, H. K. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Richter, Wiltrud |e VerfasserIn |0 (DE-588)1012822842 |0 (DE-627)704910780 |0 (DE-576)345982118 |4 aut | |
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