Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays
(2024) In EBioMedicine 104.- Abstract
BACKGROUND: Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity.
METHODS: IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly... (More)
BACKGROUND: Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity.
METHODS: IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1-10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ
2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented.
FINDINGS: The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC.
INTERPRETATION: ADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes.
FUNDING: Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and the Novo Nordisk Foundation.
(Less)
- author
- Lind, Alexander
LU
; Freyhult, Eva
; de Jesus Cortez, Felipe
; Ramelius, Anita
LU
; Bennet, Rasmus
LU
; Robinson, Peter V
; Seftel, David
; Gebhart, David
; Tandel, Devangkumar
; Maziarz, Marlena
LU
; Larsson, Helena Elding
LU
; Lundgren, Markus
LU
; Carlsson, Annelie
LU
; Nilsson, Anna-Lena
LU
; Fex, Malin
LU
; Törn, Carina
LU
; Agardh, Daniel
LU
; Tsai, Cheng-Ting
and Lernmark, Åke
LU
(Less) - author collaboration
- organization
-
- EXODIAB: Excellence of Diabetes Research in Sweden
- Celiac Disease and Diabetes Unit (research group)
- Diabetic Complications (research group)
- Paediatric Endocrinology (research group)
- Teachers at the Medical Programme
- Pediatric Autoimmunity (research group)
- Paediatrics (Lund)
- Diabetes - Molecular Metabolism (research group)
- EpiHealth: Epidemiology for Health
- publishing date
- 2024-05-08
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- EBioMedicine
- volume
- 104
- article number
- 105144
- publisher
- Elsevier
- external identifiers
-
- pmid:38723553
- ISSN
- 2352-3964
- DOI
- 10.1016/j.ebiom.2024.105144
- project
- Better Diabetes Diagnosis (BDD)
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.
- id
- c7849856-3b1c-464f-9909-280569220d02
- date added to LUP
- 2024-05-11 18:49:39
- date last changed
- 2024-05-13 09:39:37
@article{c7849856-3b1c-464f-9909-280569220d02,
abstract = {{<p>BACKGROUND: Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity.</p><p>METHODS: IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1-10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ <br>
2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented.<br>
</p><p>FINDINGS: The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC.</p><p>INTERPRETATION: ADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes.</p><p>FUNDING: Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and the Novo Nordisk Foundation.</p>}},
author = {{Lind, Alexander and Freyhult, Eva and de Jesus Cortez, Felipe and Ramelius, Anita and Bennet, Rasmus and Robinson, Peter V and Seftel, David and Gebhart, David and Tandel, Devangkumar and Maziarz, Marlena and Larsson, Helena Elding and Lundgren, Markus and Carlsson, Annelie and Nilsson, Anna-Lena and Fex, Malin and Törn, Carina and Agardh, Daniel and Tsai, Cheng-Ting and Lernmark, Åke}},
issn = {{2352-3964}},
language = {{eng}},
month = {{05}},
publisher = {{Elsevier}},
series = {{EBioMedicine}},
title = {{Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays}},
url = {{http://dx.doi.org/10.1016/j.ebiom.2024.105144}},
doi = {{10.1016/j.ebiom.2024.105144}},
volume = {{104}},
year = {{2024}},
}