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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...

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Bibliographische Detailangaben
Hauptverfasser: Söhnlein, Petra (VerfasserIn) , Müller, M. (VerfasserIn) , Syren, K. (VerfasserIn) , Hartmann, U. (VerfasserIn) , Böhm, B. O. (VerfasserIn) , Meinck, Hans-Michael (VerfasserIn) , Knip, M. (VerfasserIn) , Akerblom, H. K. (VerfasserIn) , Richter, Wiltrud (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2000
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
Volltext
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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 04.03.2021
Beschreibung:Online Resource
ISSN:1432-0428
DOI:10.1007/s001250050031

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