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

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

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

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

Dental caries status of preschool children in Hong Kong

Objective: To describe the dental caries status of preschool children in Hong Kong and factors which affect their caries status. Design: 658 preschool children aged 4 to 6 years from six randomly selected kindergartens in Hong Kong were surveyed in December 1997. A questionnaire to investigate possible explanatory variables for caries status was completed by their parents. Dental caries was diagnosed according to the criteria recommended by the World Health Organization (1997). Result: Caries experience as measured by the mean number of decayed, missing and filled primary teeth (dmft) of the 4-, 5-, and 6-year-old children were found to be 0.9, 1.8, and 3.3 respectively. Overall, 61% of the children had a zero dmft score. Children born in Mainland China had a higher mean dmft score (4.6) than those born in Hong Kong (1.4). Statistically significant correlations were found between the children's dental caries status and their oral health practices as well as their socio-economic background. Parents' education level, dental knowledge and attitudes were also associated with the children's dental caries experience. Conclusion: In general, the caries status of Hong Kong Chinese preschool children was similar to that of children in industrialised countries and was better than that of children in the nearby areas. However, special dental programmes should be made available to children from lower socio-economic classes and new immigrants from Mainland China because they are the high risk groups for caries in Hong Kong. © British Dental Journal 1999.link_to_OA_fulltex