Overview
Sian completed her MSc degree at the University of the West of England (Bristol) in 2015 where she specialized in blood sciences. Following her interest in autoimmune disorders, she took up a technician role in the European Islet Autoantibody Reference Laboratory based in the Diabetes and Metabolism group at the University of Bristol. Sian subsequently moved into a research technician role specializing in developing novel non-radioactive high-throughput methods for the detection of these islet autoantibodies.
Sian joined the University of Exeter in September 2019 after being awarded an E3 PhD Studentship. Sian’s PhD research; working with Dr Angus Jones; is focused on improving adult diagnosis of Type 1 Diabetes using islet autoantibodies.
Qualifications
- MSc Biomedical Sciences (Blood Sciences)
- BSc Applied Biomedical Sciences (Clinical)
Grants/Funding:
Research
Research interests
Previously Sian has been involved in the development of novel luciferase based assay systems for the detection of islet autoantibodies. Her research involved creating small volume, multiplexed and alternative format assays with enhanced sensitivity and specificity.
Her PhD with Dr Angus Jones will involve improving the clinical utility of islet autoantibodies with a focus on improving classification and diagnosis of diabetes in adults.
Research projects
Current Projects:
- Improving Adult Diagnosis of Type 1 Diabetes using Islet Autoantibodies
Publications
Key publications | Publications by category | Publications by year
Publications by category
Journal articles
Kaur A, Grace SL, Bowden J, Walkey HC, Misra S, Shields BM, McKinley TJ, Oliver NS, McDonald TJ, Johnston DG, et al (2022). Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association with Genetic and Clinical Characteristics.
J Clin Endocrinol Metab,
107(12), e4341-e4349.
Abstract:
Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association with Genetic and Clinical Characteristics.
CONTEXT: the importance of the autoantibody level at diagnosis of type 1 diabetes (T1D) is not clear. OBJECTIVE: We aimed to assess the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) autoantibody levels with clinical and genetic characteristics at diagnosis of T1D. METHODS: We conducted a prospective, cross-sectional study. GADA, IA-2A, and ZnT8A were measured in 1644 individuals with T1D at diagnosis using radiobinding assays. Associations between autoantibody levels and the clinical and genetic characteristics for individuals were assessed in those positive for these autoantibodies. We performed replication in an independent cohort of 449 people with T1D. RESULTS: GADA and IA-2A levels exhibited a bimodal distribution at diagnosis. High GADA level was associated with older age at diagnosis (median 27 years vs 19 years, P = 9 × 10-17), female sex (52% vs 37%, P = 1 × 10-8), other autoimmune diseases (13% vs 6%, P = 3 × 10-6), and HLA-DR3-DQ2 (58% vs 51%, P =. 006). High IA-2A level was associated with younger age of diagnosis (median 17 years vs 23 years, P = 3 × 10-7), HLA-DR4-DQ8 (66% vs 50%, P = 1 × 10-6), and ZnT8A positivity (77% vs 52%, P = 1 × 10-15). We replicated our findings in an independent cohort of 449 people with T1D where autoantibodies were measured using enzyme-linked immunosorbent assays. CONCLUSION: Islet autoantibody levels provide additional information over positivity in T1D at diagnosis. Bimodality of GADA and IA-2A autoantibody levels highlights the novel aspect of heterogeneity of T1D. This may have implications for T1D prediction, treatment, and pathogenesis.
Abstract.
Author URL.
Grace SL, Cooper A, Jones AG, McDonald TJ (2021). Zinc transporter 8 autoantibody testing requires age-related cut-offs.
BMJ Open Diabetes Research & Care,
9(1), e002296-e002296.
Abstract:
Zinc transporter 8 autoantibody testing requires age-related cut-offs
IntroductionZinc transporter 8 autoantibodies (ZnT8A) are biomarkers of beta cell autoimmunity in type 1 diabetes that have become more widely available to clinicians in recent years. Robust control population-defined thresholds are essential to ensure high clinical specificity in islet autoantibody testing. We aimed to determine the optimal cut-offs for ZnT8A testing.Research design and methods97.5th and 99th centile cut-offs were determined using residual clinical sera from 1559 controls aged between 0 and 83 years with no history of diabetes and a hemoglobin A1c level of less than 6.0% (<42 mmol/mol). ZnT8A were measured by ELISA (RSR, Cardiff, UK) on a Dynex DS2 ELISA robot (Dynex, Preston, UK). We assessed the impact of age-related cut-offs in comparison with the manufacturer’s recommended threshold in a mixed cohort of young-onset (<age 30) diabetes (UNITED study (Using pharmacogeNetics to Improve Treatment in Early-onset Diabetes), n=145).ResultsUsing the manufacturer’s limit of detection, 6 WHO U/mL, 16.2% of people in the control cohort had detectable levels of ZnT8A and those who had detectable ZnT8A were much more likely to be younger (p<0.0001). The 97.5th and 99th centile thresholds were substantially higher in younger participants: 18 and 127 WHO U/mL (tested under 30 years) in comparison with 9 and 21 WHO U/mL (tested 30 years and over). In the UNITED cohort some of those found to be ZnT8A-positive by the manufacturer’s threshold but negative using the appropriate 99% centile cut-off (127 WHO U/mL) displayed characteristics suggestive of type 2 diabetes.ConclusionsAge-related thresholds are needed for ZnT8A testing. In those aged <30 years, use of manufacturers’ recommended cut-offs may result in low test specificity and potentially high rates of false positive test results in patients who do not have autoimmune diabetes.
Abstract.
Conferences
Grace SL, Cooper A, Jones AG, McDonald TJ (2020). Zinc transporter 8 autoantibody testing requires age-specific cut-offs.
Author URL.
Publications by year
2022
Kaur A, Grace SL, Bowden J, Walkey HC, Misra S, Shields BM, McKinley TJ, Oliver NS, McDonald TJ, Johnston DG, et al (2022). Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association with Genetic and Clinical Characteristics.
J Clin Endocrinol Metab,
107(12), e4341-e4349.
Abstract:
Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association with Genetic and Clinical Characteristics.
CONTEXT: the importance of the autoantibody level at diagnosis of type 1 diabetes (T1D) is not clear. OBJECTIVE: We aimed to assess the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) autoantibody levels with clinical and genetic characteristics at diagnosis of T1D. METHODS: We conducted a prospective, cross-sectional study. GADA, IA-2A, and ZnT8A were measured in 1644 individuals with T1D at diagnosis using radiobinding assays. Associations between autoantibody levels and the clinical and genetic characteristics for individuals were assessed in those positive for these autoantibodies. We performed replication in an independent cohort of 449 people with T1D. RESULTS: GADA and IA-2A levels exhibited a bimodal distribution at diagnosis. High GADA level was associated with older age at diagnosis (median 27 years vs 19 years, P = 9 × 10-17), female sex (52% vs 37%, P = 1 × 10-8), other autoimmune diseases (13% vs 6%, P = 3 × 10-6), and HLA-DR3-DQ2 (58% vs 51%, P =. 006). High IA-2A level was associated with younger age of diagnosis (median 17 years vs 23 years, P = 3 × 10-7), HLA-DR4-DQ8 (66% vs 50%, P = 1 × 10-6), and ZnT8A positivity (77% vs 52%, P = 1 × 10-15). We replicated our findings in an independent cohort of 449 people with T1D where autoantibodies were measured using enzyme-linked immunosorbent assays. CONCLUSION: Islet autoantibody levels provide additional information over positivity in T1D at diagnosis. Bimodality of GADA and IA-2A autoantibody levels highlights the novel aspect of heterogeneity of T1D. This may have implications for T1D prediction, treatment, and pathogenesis.
Abstract.
Author URL.
2021
Grace SL, Cooper A, Jones AG, McDonald TJ (2021). Zinc transporter 8 autoantibody testing requires age-related cut-offs.
BMJ Open Diabetes Research & Care,
9(1), e002296-e002296.
Abstract:
Zinc transporter 8 autoantibody testing requires age-related cut-offs
IntroductionZinc transporter 8 autoantibodies (ZnT8A) are biomarkers of beta cell autoimmunity in type 1 diabetes that have become more widely available to clinicians in recent years. Robust control population-defined thresholds are essential to ensure high clinical specificity in islet autoantibody testing. We aimed to determine the optimal cut-offs for ZnT8A testing.Research design and methods97.5th and 99th centile cut-offs were determined using residual clinical sera from 1559 controls aged between 0 and 83 years with no history of diabetes and a hemoglobin A1c level of less than 6.0% (<42 mmol/mol). ZnT8A were measured by ELISA (RSR, Cardiff, UK) on a Dynex DS2 ELISA robot (Dynex, Preston, UK). We assessed the impact of age-related cut-offs in comparison with the manufacturer’s recommended threshold in a mixed cohort of young-onset (<age 30) diabetes (UNITED study (Using pharmacogeNetics to Improve Treatment in Early-onset Diabetes), n=145).ResultsUsing the manufacturer’s limit of detection, 6 WHO U/mL, 16.2% of people in the control cohort had detectable levels of ZnT8A and those who had detectable ZnT8A were much more likely to be younger (p<0.0001). The 97.5th and 99th centile thresholds were substantially higher in younger participants: 18 and 127 WHO U/mL (tested under 30 years) in comparison with 9 and 21 WHO U/mL (tested 30 years and over). In the UNITED cohort some of those found to be ZnT8A-positive by the manufacturer’s threshold but negative using the appropriate 99% centile cut-off (127 WHO U/mL) displayed characteristics suggestive of type 2 diabetes.ConclusionsAge-related thresholds are needed for ZnT8A testing. In those aged <30 years, use of manufacturers’ recommended cut-offs may result in low test specificity and potentially high rates of false positive test results in patients who do not have autoimmune diabetes.
Abstract.
2020
Grace SL, Cooper A, Jones AG, McDonald TJ (2020). Zinc transporter 8 autoantibody testing requires age-specific cut-offs.
Author URL.
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