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Wyatt, R.C.* ; Grace, S.L.* ; Brigatti, C.* ; Marzinotto, I.* ; Gillard, B.T.* ; Shoemark, D.K.* ; Chandler, K.* ; Achenbach, P. ; Piemonti, L.* ; Long, A.E.* ; Gillespie, K.M.* ; Lampasona, V.* ; Williams, A.J.K.*

Improved specificity of glutamate decarboxylase 65 autoantibody measurement using luciferase-based immunoprecipitation system (LIPS) assays.

Diabetes 73, 565-571 (2024)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Autoantibodies to glutamate decarboxylase (GADA) are widely used in the prediction and classification of type 1 diabetes. GADA radiobinding assays (RBAs) using N-terminally truncated antigens offer improved specificity but radioisotopes limit the high-throughput potential for population screening. Luciferase-based Immunoprecipitation System (LIPS) assays are sensitive and specific alternatives to RBAs with the potential to improve risk stratification. The performance of assays using the Luciferase (Nluc-) conjugated GAD65 constructs, Nluc-GAD65(96-585) and full length Nluc-GAD65(1-585) were evaluated in 434 well-characterised sera from recent-onset type 1 diabetes patients and first-degree relatives. Non-radioactive, high-throughput LIPS assays are quicker and require less serum than RBAs. Of 171 relatives previously tested single autoantibody positive for autoantibodies to full-length GAD65 by RBA but had not progressed to diabetes, fewer retested positive by LIPS using either truncated (n=72) or full-length (n=111) antigen. The Nluc-GAD65(96-585) truncation demonstrated the highest specificity in LIPS assays overall but in contrast to RBA, N-terminus truncations did not result in a significant increase in disease-specificity compared with the full-length antigen. This suggests that binding of non-specific antibodies is affected by the conformational changes resulting from addition of the Nluc antigen. Nluc-GAD65(96-585) LIPS assays offer low blood volume, high specificity GADA tests for screening and diagnostics.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Zeitschrift Diabetes
Quellenangaben Band: 73, Heft: 4, Seiten: 565-571 Artikelnummer: , Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, VA.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research (IDF)