Sensitive detection of multiple islet autoantibodies in type 1 diabetes using small sample volumes by agglutination-PCR
Autor: | Jordan Owyoung, Andrew McKeon, Cheng-ting Tsai, Darrell M. Wilson, Bruce A. Buckingham, Srinath Sanda, Cate Speake, David M. Maahs, Peter V. Robinson, Matthew M. Roforth, Narges Pourmandi, Kara Page, Felipe de Jesus Cortez, David Gebhart, Carla J. Greenbaum, Sean J. Pittock, Wendy A. Wolf, John Mills, David Seftel, Carolyn R. Bertozzi |
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Přispěvatelé: | Chatenoud, Lucienne |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Physiology Epidemiology medicine.medical_treatment Insulin Antibodies Artificial Gene Amplification and Extension Polymerase Chain Reaction Biochemistry 0302 clinical medicine Endocrinology Medical Conditions Immune Physiology Medicine and Health Sciences Medicine Mass Screening Insulin Bile Multiplex Pediatric Multidisciplinary geography.geographical_feature_category Immune System Proteins biology Glutamate Decarboxylase Diabetes Islet Body Fluids Female Antibody Anatomy 4.2 Evaluation of markers and technologies Type 1 Research Article Adult Agglutination Adolescent General Science & Technology Endocrine Disorders Science Concordance Immunology 030209 endocrinology & metabolism Research and Analysis Methods Autoimmune Disease Sensitivity and Specificity Antibodies 03 medical and health sciences Islets of Langerhans Young Adult Diabetes Mellitus Humans Molecular Biology Techniques Molecular Biology Metabolic and endocrine Autoantibodies Diabetic Endocrinology Type 1 diabetes geography Endocrine Physiology business.industry Insulin Signaling Autoantibody Biology and Life Sciences Proteins Bilirubin medicine.disease Hormones 4.1 Discovery and preclinical testing of markers and technologies Agglutination (biology) 030104 developmental biology Diabetes Mellitus Type 1 Metabolic Disorders Medical Risk Factors biology.protein business |
Zdroj: | PLoS ONE PloS one, vol 15, iss 11 PLoS ONE, Vol 15, Iss 11, p e0242049 (2020) |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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