Projects per year
Aim: Persistence of autoantibodies after diagnosis may reflect ongoing beta-cell destruction but little is known about what factors influence this. Previously, we demonstrated that the principal predictor of a persistent ZnT8A response after diabetes onset, was a high titre at diagnosis, independent of T1D-associated genetic and non-genetic determinants. Here, we investigate whether the presence of autoantibodies to glutamate decarboxylase (GADA), islet antigen-2 (IA-2A) or insulin (IAA) at diagnosis influences ZnT8A persistence. Methods: ZnT8A positive individuals with T1D [n=214; 121 males; median age at diagnosis 10.19yrs (range 0.7-21yrs)] who had a first sample close to diabetes onset [median time from diagnosis, 0yrs (range -0.9 to 2.0yrs)] and a sample after diagnosis (range 1.9-32.20yrs) were tested for GADA, IA-2A and IAA (n=146; samples within 14 days of diagnosis) using established methods. Multivariate logistic regression models (SPSS) including time of the last sample, number of autoantibodies, ZnT8A titre at diagnosis and T1D-associated HLA Class I (A*24, B*18 and B*39) and Class II (DR3/DR4) genetics were then applied. Results: Presence of GADA (p=0.001) independent of GADA titre (p=0.426) or positivity for IA-2A and/or IAA at diagnosis was associated with ZnT8A persistence. This effect was independent of genetic determinants (p=0.001), ZnT8A titre at diagnosis (p<0.001) and other factors. Gender modifies this effect after correction for HLA (p=0.030). Conclusions: Co-expression of ZnT8A with GADA identifies individuals who are more likely to maintain their ZnT8A humoral response after diagnosis. The complex interactions that determine ZnT8A persistence provides further insight into the time course and regulation of beta-cell destruction.
|Publication status||Published - 6 Mar 2019|
|Event||Diabetes UK Professional Conference 2019 - Liverpool, United Kingdom, Liverpool, United Kingdom|
Duration: 6 Mar 2019 → 8 Mar 2019
|Conference||Diabetes UK Professional Conference 2019|
|Period||6/03/19 → 8/03/19|
FingerprintDive into the research topics of 'Autoantibodies to zinc transporter 8 (ZnT8A) are more likely to persist after diagnosis in the presence of co-existing autoantibodies to glutamate decarboxylase (GADA) at type 1 diabetes onset.'. Together they form a unique fingerprint.
- 1 Finished
The natural history of the autoimmune response to zinc transporter 8 in type 1 diabetes (PhD; Diabetes UK funded)
2/10/17 → 10/10/21