title: Islet Autoantibody Measurements from Dried Blood Spots on Filter Paper Strongly Correlate to Serum Levels.
abstract: Type 1 diabetes (T1D) is increasing in incidence and predictable with measurement of serum islet autoantibodies (iAb) years prior to clinical disease onset. Identifying iAb positive individuals reduces diabetic ketoacidosis and identifies individuals for T1D prevention trials. However, large scale screening for iAb remains challenging as assays have varying sensitivities and specificities, insulin autoantibodies remain difficult to measure and venipuncture is generally required to obtain serum. We developed an approach to reliably measure all four major iAb, including insulin autoantibodies, from dried blood spots (DBS) on filter-paper. By spiking iAb positive serum into iAb negative whole blood in a dose titration, we optimized the conditions for autoantibody elution from filter paper as measured by fluid phase radioimmunoassays. After assessing stability of measuring iAb from DBS over time, we then screened iAb from DBS and the corresponding serum in new-onset T1D (n = 52), and controls (n = 72) which included first-degree relatives of T1D patients. iAb measured from eluted DBS in new-onset T1D strongly correlated with serum measurements (R2 = 0.96 for mIAA, GADA = 0.94, IA-2A = 0.85, ZnT8A = 0.82, p<0.01 for each autoantibody). There were no false positives in control subjects, and 5/6 with previously unknown iAb positivity in sera were detected using DBS. With further validation, measuring iAb from DBS can be a reliable method to screen for T1D risk.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 80045, United States of America.
authors.forename: Kimber M
authors.initials: KM
authors.lastname: Simmons
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 80045, United States of America.
authors.forename: Aimon K
authors.initials: AK
authors.lastname: Alkanani
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 80045, United States of America.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: McDaniel
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, 46202, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Goyne
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 80045, United States of America.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 80045, United States of America.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 80045, United States of America.
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 80045, United States of America.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: Michels
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology; D059788:Dried Blood Spot Testing; D005260:Female; D006801:Humans; D007330:Insulin Antibodies / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay / Q000379:methods
chemical_list: D001323:Autoantibodies; D007330:Insulin Antibodies