3 Screen islet cell autoantibody ELISA: A sensitive and specific ELISA for the combined measurement of autoantibodies to GAD65, to IA-2 and to ZnT8

Amoroso, Marie; Achenbach, Peter; Powell, Michael J.; Coles, Rebecca; Chlebowska, Monika; Carr, Lorraine; Furmaniak, Jadwiga; Scholz, Marlon; Bonifacio, Ezio; Ziegler, Anette‐G.; Smith, Bernard Rees

doi:10.1016/j.cca.2016.08.013

Cited by 29 publications

(28 citation statements)

References 20 publications

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“…Autoantibody tests for GAD65, IA-2 and ZnT8 were repeated in another laboratory (Helmholtz Institute, Munich, Germany) using internationally standardized and evaluated assays 31 . These included the 3-Screen enzyme-linked immunosorbent assay (ELISA) that measures antibodies against GAD65, IA-2 and ZnT8 (RSR) 32 , and radiobinding immunoprecipitation assays with [ 35 S]methionine-labelled recombinant human proteins measuring antibodies against GAD65, IA-2 and ZnT8 (refs. 33,34 ).…”

Section: Methodsmentioning

confidence: 99%

Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report

Hollstein¹,

Schulte²,

Wagner³

et al. 2020

Nat Metab

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162

145

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Here we report a case where the manifestations of insulin-dependent diabetes occurred following SARS-CoV-2 infection in a young individual in the absence of autoantibodies typical for type 1 diabetes mellitus. Specifically, a 19-year-old white male presented at our emergency department with diabetic ketoacidosis, C-peptide level of 0.62 µg l-1 , blood glucose concentration of 30.6 mmol l-1 (552 mg dl-1) and haemoglobin A1c of 16.8%. The patient´s case history revealed probable COVID-19 infection 5-7 weeks before admission, based on a positive test for antibodies against SARS-CoV-2 proteins as determined by enzyme-linked immunosorbent assay. Interestingly, the patient carried a human leukocyte antigen genotype (HLA DR1-DR3-DQ2) considered to provide only a slightly elevated risk of developing autoimmune type 1 diabetes mellitus. However, as noted, no serum autoantibodies were observed against islet cells, glutamic acid decarboxylase, tyrosine phosphatase, insulin and zinc-transporter 8. Although our report cannot fully establish causality between COVID-19 and the development of diabetes in this patient, considering that SARS-CoV-2 entry receptors, including angiotensin-converting enzyme 2, are expressed on pancreatic β-cells and, given the circumstances of this case, we suggest that SARS-CoV-2 infection, or COVID-19, might negatively affect pancreatic function, perhaps through direct cytolytic effects of the virus on β-cells. The recent COVID-19 pandemic caused by the SARS-CoV-2 virus represents a worldwide health crisis causing severe illness and death, especially in people with cardiovascular and metabolic abnormalities 1,2. SARS-CoV-2 enters human cells via angiotensinconverting enzyme 2 (ACE2) 3 , a transmembrane glycoprotein with proteolytic activity also found in human pancreatic β-cells 4 , suggesting that SARS-CoV-2 might alter pancreatic β-cell function and impair insulin secretion. Several recently published studies indicate a link between COVID-19 and diabetes: for example, acute hyper glycaemia has been observed in a large number of individuals infected with SARS-CoV-2, regardless of any past medical history of diabetes 5-8. In another study in Asia, patients were reported

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Section: Methodsmentioning

confidence: 99%

Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report

Hollstein¹,

Schulte²,

Wagner³

et al. 2020

Nat Metab

Self Cite

162

145

View full text Add to dashboard Cite

show abstract

“…Cost is a clear factor, because population‐based screening requires that tens or hundreds of thousands of children be tested, more than 99% of whom will be negative. This will require a sensitive first‐line test that covers the majority of the major islet autoantibodies (IAA, GADA, IA‐2A, ZnT8A), with follow‐up tests for those who are positive to confirm and stratify their risk . Point‐of‐care testing may be one approach to achieving this.…”

Section: The Futurementioning

confidence: 99%

Birth and coming of age of islet autoantibodies

Bonifacio

Achenbach

2019

Clinical and Experimental Immunology

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“…Apart from ADAP, several research groups have developed and implemented non-radioactive assays for islet autoantibody measurement. Multiplex ELISA (also known as the threescreen ELISA) relies on a familiar ELISA workflow and instrumentation [8,25]. It generates a single composite signal in the presence of GAD, IA-2 or ZnT8 autoantibodies.…”

Section: Plos Onementioning

confidence: 99%

“…Alternative methods such as ELISAs have been developed to address some of the limitations of radioassay; however, they do not detect insulin autoantibodies, one of the earliest biomarkers for type 1 diabetes, and still consume 20-50 μL of serum per autoantibody [6][7][8]. Other multiplex approaches such as nanoparticle enhanced immunoassays and electrochemical luminescence (ECL) assays require specialized instrumentation for assay readout, sample pretreatment or longer time-to-result (>16 hr) [5,[9][10][11][12][13].…”

Section: Introductionmentioning

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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3 Screen islet cell autoantibody ELISA: A sensitive and specific ELISA for the combined measurement of autoantibodies to GAD65, to IA-2 and to ZnT8

Cited by 29 publications

References 20 publications

Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report

Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report

Birth and coming of age of islet autoantibodies

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

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