Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes

• Verfasst von: Söhnlein, Petra [VerfasserIn]
• Verfasst von: Müller, M. [VerfasserIn]
• Verfasst von: Syren, K. [VerfasserIn]
• Verfasst von: Hartmann, U. [VerfasserIn]
• Verfasst von: Böhm, B. O. [VerfasserIn]
• Verfasst von: Meinck, Hans-Michael [VerfasserIn]
• Verfasst von: Knip, M. [VerfasserIn]
• Verfasst von: Akerblom, H. K. [VerfasserIn]
• Verfasst von: Richter, Wiltrud [VerfasserIn]
• Titel: Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes
• Verf.angabe: 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
• Jahr: 2000
• Umfang: 8 S.
• Teil: volume:43
• Teil: year:2000
• Teil: number:2
• Teil: pages:210-217
• Teil: extent:8
• Fussnoten: Gesehen am 04.03.2021
• Titel Quelle: Enthalten in: Diabetologia
• Ort Quelle: Berlin : Springer, 1965
• Jahr Quelle: 2000
• Band/Heft Quelle: 43(2000), 2, Seite 210-217
• ISSN Quelle: 1432-0428
• DOI: doi:10.1007/s001250050031
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1750414414

Abstract

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.