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Med."],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate whether the N\u2010terminal truncated glutamic acid decarboxylase 65 (<jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65) isoform is as well recognized by people with stiff person syndrome as it is by people with Type 1 diabetes, and whether conformational <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65 antibody epitopes are displayed properly by the isoform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65 antibody\u2010positive healthy individuals (<jats:italic>n<\/jats:italic>=13), people with stiff\u2010person syndrome (<jats:italic>n<\/jats:italic>=15) and children with new\u2010onset Type 1 diabetes (<jats:italic>n<\/jats:italic>=654) were analysed to determine binding to full\u2010length <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65 and the N\u2010terminal truncated <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65 isoform in each of these settings. <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65 autoantibody epitope specificity was correlated with binding ratios of full\u2010length <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65\/N\u2010terminal truncated <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The N\u2010terminal truncated <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65 isoform was significantly less recognized in <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65Ab\u2010positive people with stiff\u2010person syndrome (<jats:italic>P<\/jats:italic>=0.002) and in healthy individuals (<jats:italic>P<\/jats:italic>=0.0001) than in people with Type 1 diabetes. Moreover, at least two specific conformational <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65Ab epitopes were not, or were only partially, presented by the N\u2010terminal truncated <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65 isoform compared to full\u2010length <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65. Finally, an N\u2010terminal conformational <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65Ab epitope was significantly less recognized in <jats:styled-content style=\"fixed-case\">DQ<\/jats:styled-content>8\/8 positive individuals with Type 1 diabetes (<jats:italic>P<\/jats:italic>=0.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In people with stiff person syndrome preferred binding to the full\u2010length <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65 isoform over the N\u2010terminal truncated molecule was observed. This binding characteristic is probably attributable to reduced presentation of two conformational epitopes by the N\u2010terminal truncated molecule. These findings support the notion of disease\u2010specific <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>65Ab epitope specificities and emphasize the need to evaluate the applicability of novel assays for different medical conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.13827","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T06:11:08Z","timestamp":1538115068000},"page":"1375-1383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Reduced display of conformational epitopes in the N\u2010terminal truncated <scp>GAD<\/scp>65 isoform: relevance for people with stiff person syndrome or <scp>DQ<\/scp>8\/8\u2010positive Type 1 diabetes mellitus"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9111-6671","authenticated-orcid":false,"given":"C. 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