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Titolo:
Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes
Autore:
Sohnlein, P; Muller, M; Syren, K; Hartmann, U; Bohm, BO; Meinck, HM; Knip, M; Akerblom, HK; Richter, W;
Indirizzi:
Univ Heidelberg, Dept Orthopaed Surg, Heidelberg, Germany Univ HeidelbergHeidelberg Germany Orthopaed Surg, Heidelberg, Germany Univ Ulm, Dept Internal Med 1, D-7900 Ulm, Germany Univ Ulm Ulm Germany D-7900 lm, Dept Internal Med 1, D-7900 Ulm, Germany Univ Heidelberg, Dept Clin Neurol, Heidelberg, Germany Univ Heidelberg Heidelberg Germany ept Clin Neurol, Heidelberg, Germany Univ Tampere, Sch Med, FIN-33101 Tampere, Finland Univ Tampere Tampere Finland FIN-33101 h Med, FIN-33101 Tampere, Finland Tampere Univ Hosp, Dept Paediat, Tampere, Finland Tampere Univ Hosp Tampere Finland Hosp, Dept Paediat, Tampere, Finland Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland Univ Helsinki Helsinki Finland hildren & Adolescents, Helsinki, Finland
Titolo Testata:
DIABETOLOGIA
fascicolo: 2, volume: 43, anno: 2000,
pagine: 210 - 217
SICI:
0012-186X(200002)43:2<210:ESAAVB>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTAMIC-ACID DECARBOXYLASE; STIFF-MAN SYNDROME; ISLET-CELL ANTIBODIES; AUTOANTIBODIES; MELLITUS; IDENTIFICATION; AUTOANTIGEN; RELATIVES; CHILDREN; ANTIGEN;
Keywords:
glutamate decarboxylase; autoantibodies; epitope-specificity; Type I diabetes; polyendocrine autoimmune syndrome; stiff-man syndrome; prediabetes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Richter, W Univ Heidelberg, Stiftung Orthopad Klin, Schlierbacher Landstr 200A, D-69118 Heidelberg, Germany Univ Heidelberg Schlierbacher Landstr 200A Heidelberg Germany D-69118
Citazione:
P. Sohnlein et al., "Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes", DIABETOLOG, 43(2), 2000, pp. 210-217

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 epitopesor 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/21 alle ore 03:31:33