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
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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