Islet autoantibody status in a multi-ethnic UK clinic cohort of children presenting with diabetes

Perchard, Reena; MacDonald, Don; Say, Jemma; Pitts, JE; Pye, Stephen R.; Allgrove, Jeremy; Banerjee, Kausik; Amin, Rakesh

doi:10.1136/archdischild-2014-306542

Cited by 8 publications

(6 citation statements)

References 21 publications

(29 reference statements)

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“…IAA assay has a sensitivity of 95% and specialty of 36%. Insulin auto antibodies were detected in 36% of our patients and this falls in the lower limit of figures of 40-70% reported in literature [5][6][7][8]14,15]. It is similar to data from Saudi Arabia [16] and Japan [17] but lower than figures of 69% [18] and 50% reported from UK and Tunisia [11,18] respectively.…”

Section: Discussionsupporting

confidence: 83%

Pancreatic Autoantibodies in Sudanese Children with Newly Diagnosed Type 1 Diabetes Mellitus

Rabab¹,

Urwa²,

Abdullah³

2019

Int J Diabetes Clin Res

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Background: Immunepositive type one diabetes mellitus is the commonest cause of diabetes in children worldwide. Seronegative cases are said to be more common among black Africans. In a previous study in Sudan 46% of cases were found to have positive GAD antibodies. Objectives of the study: The aim of this study was to find out the prevalence of pancreatic autoantibodies among multiethnic group of newly diagnosed Sudanese children by testing for multiple antibodies and to see how common are seronegative cases as reported in black Africans. Subjects and methods: Eighty newly diagnosed children aged (1-18 years) of multiethnic groups with clinical diagnosis of type 1 diabetes mellitus were tested for 3 islet cell antibodies Glutamic Acid Decarboxylose (GADA), insulin autoantibodies (IAA) and Zinc Transporter (ZNT8A) using ELISA (ZNT8M GADA) and Radioimmunoassay (RIA) for IAA. Demographic and clinical data were obtained from the records-clinical presentations of the….seronegative cases was compared with the seropositive cases. Results: A positive result for one or more antibodies was found in 73 (91.2%) and negative in 7 (8.8%) of the cases-No ethnic variation was demonstrated. There was no difference in the clinical presentation of the two group. IAA was positive in 29 (36.3%), GADA in 62 (77.5%) and ZNT8A in 13 (16.3%). On testing for two antibodies, the best yield was on combining GADA and IAA 61 (76.3%). Conclusion: Unlike the previous study from Sudan most (91.2%) of Sudanese children with Type 1 diabetes have got one or more pancreatic antibodies at onset. However 8.2% are seronegative. Further studies to find the causes in this seronegative group is needed.

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Section: Discussionsupporting

confidence: 83%

Pancreatic Autoantibodies in Sudanese Children with Newly Diagnosed Type 1 Diabetes Mellitus

Rabab¹,

Urwa²,

Abdullah³

2019

Int J Diabetes Clin Res

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“… 16 17 Reports of the variation of autoantibody status and frequency with ethnicity are also scarce and have revealed a somewhat conflicting picture. 6 18–20 Differences in presenting features of T1D with autoantibody status warrant further investigation in children and adults in the multiethnic UK population to improve understanding of the heterogeneity of T1D. People with T1D have a lifelong dependency on treatment with exogenous insulin, resulting from an autoimmune destruction of pancreatic beta cells.…”

Section: Introductionmentioning

confidence: 99%

Rationale and protocol for the After Diabetes Diagnosis REsearch Support System (ADDRESS): an incident and high risk type 1 diabetes UK cohort study

et al. 2017

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IntroductionType 1 diabetes is heterogeneous in its presentation and progression. Variations in clinical presentation between children and adults, and with ethnic group warrant further study in the UK to improve understanding of this heterogeneity. Early interventions to limit beta cell damage in type 1 diabetes are undergoing evaluation, but recruitment is challenging. The protocol presented describes recruitment of people with clinician-assigned, new-onset type 1 diabetes to understand the variation in their manner of clinical presentation, to facilitate recruitment into intervention studies and to create an open-access resource of data and biological samples for future type 1 diabetes research.Methods and analysisUsing the National Institute for Health Research Clinical Research Network, patients >5 years of age diagnosed clinically with type 1 diabetes (and their siblings) are recruited within 6 months of diagnosis. Participants agree to have their clinical, laboratory and demographic data stored on a secure database, for their clinical progress to be monitored using information held by NHS Digital, and to be contacted about additional research, in particular immunotherapy and other interventions. An optional blood sample is taken for islet autoantibody measurement and storage of blood and DNA for future analyses. Data will be analysed statistically to describe the presentation of incident type 1 diabetes in a contemporary UK population.Ethics and disseminationEthical approval was obtained from the independent NHS Research Ethics Service. Results will be presented at national and international meetings and submitted for publication to peer-reviewed journals.

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“…It was noted that the control groups had differences in age, gender or races than the cases for few of the cohorts. Since the prevalence of islet autoantibodies was minimally dependent on these factors [23,24], the difference should have marginal impact on the observed sensitivity and specificity. Indeed, the high sensitivities and specificities of the assay were observed in several well matched cohorts, such as the fully matched IASP 2018 study (cohort 2).…”

Section: Discussionmentioning

confidence: 99%

Sensitive detection of multiple islet autoantibodies in type 1 diabetes using small sample volumes by agglutination-PCR

Cortez¹,

Gebhart²,

Robinson³

et al. 2020

PLoS ONE

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Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We developed a multiplex analysis platform based on antibody detection by agglutination-PCR (ADAP) for the sample-sparing measurement of GAD, IA-2 and insulin autoantibodies/antibodies in 1 μL serum. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. The average overall agreement between ADAP and radioassay was above 91%. The average clinical sensitivity and specificity were 96% and 97%. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. Furthermore, ADAP correctly identified 95% high-risk individuals with two or more autoantibodies by radioassay amongst 39 relatives of T1D patients tested. In conclusion, the new ADAP assay can reliably detect the three cardinal islet autoantibodies/antibodies in 1μL serum with high sensitivity. This novel assay may improve pediatric testing compliance and facilitate easier community-wide screening for islet autoantibodies.

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Islet autoantibody status in a multi-ethnic UK clinic cohort of children presenting with diabetes

Cited by 8 publications

References 21 publications

Pancreatic Autoantibodies in Sudanese Children with Newly Diagnosed Type 1 Diabetes Mellitus

Pancreatic Autoantibodies in Sudanese Children with Newly Diagnosed Type 1 Diabetes Mellitus

Rationale and protocol for the After Diabetes Diagnosis REsearch Support System (ADDRESS): an incident and high risk type 1 diabetes UK cohort study

Sensitive detection of multiple islet autoantibodies in type 1 diabetes using small sample volumes by agglutination-PCR

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