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Reduced display of conformational epitopes in the N-terminal truncated GAD65 isoform: relevance for people with stiff person syndrome or DQ8/8-positive Type 1 diabetes mellitus
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2019 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 36, no 11, p. 1375-1383Article in journal (Refereed) Published
Abstract [en]

Aims: To investigate whether the N‐terminal truncated glutamic acid decarboxylase 65 (GAD65) isoform is as well recognized by people with stiff person syndrome as it is by people with Type 1 diabetes, and whether conformational GAD65 antibody epitopes are displayed properly by the isoform.

Methods: GAD65 antibody‐positive healthy individuals (n=13), people with stiff‐person syndrome (n=15) and children with new‐onset Type 1 diabetes (n=654) were analysed to determine binding to full‐length GAD65 and the N‐terminal truncated GAD65 isoform in each of these settings. GAD65 autoantibody epitope specificity was correlated with binding ratios of full‐length GAD65/N‐terminal truncated GAD65.

Results: The N‐terminal truncated GAD65 isoform was significantly less recognized in GAD65Ab‐positive people with stiff‐person syndrome (P=0.002) and in healthy individuals (P=0.0001) than in people with Type 1 diabetes. Moreover, at least two specific conformational GAD65Ab epitopes were not, or were only partially, presented by the N‐terminal truncated GAD65 isoform compared to full‐length GAD65. Finally, an N‐terminal conformational GAD65Ab epitope was significantly less recognized in DQ8/8 positive individuals with Type 1 diabetes (P=0.02).

Conclusions: In people with stiff person syndrome preferred binding to the full‐length GAD65 isoform over the N‐terminal truncated molecule was observed. This binding characteristic is probably attributable to reduced presentation of two conformational epitopes by the N‐terminal truncated molecule. These findings support the notion of disease‐specific GAD65Ab epitope specificities and emphasize the need to evaluate the applicability of novel assays for different medical conditions.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019. Vol. 36, no 11, p. 1375-1383
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Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:umu:diva-164971DOI: 10.1111/dme.13827ISI: 000491006800008PubMedID: 30264481OAI: oai:DiVA.org:umu-164971DiVA, id: diva2:1369505
Available from: 2019-11-12 Created: 2019-11-12 Last updated: 2019-11-12Bibliographically approved

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Rolandsson, Olov

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