Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays

Alexander Lind; Eva Freyhult; Felipe de Jesus Cortez; Anita Ramelius; Rasmus Bennet; Peter V Robinson; David Seftel; David Gebhart; Devangkumar Tandel; Marlena Maziarz; Helena Elding Larsson; Markus Lundgren; Annelie Carlsson; Anna-Lena Nilsson; Malin Fex; Carina Törn; Daniel Agardh; Cheng-Ting Tsai; Åke Lernmark; Better Diabetes Diagnosis (BDD) Study Group

doi:10.1016/j.ebiom.2024.105144

Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays

Alexander Lind, Eva Freyhult, Felipe de Jesus Cortez, Anita Ramelius, Rasmus Bennet, Peter V Robinson, David Seftel, David Gebhart, Devangkumar Tandel, Marlena Maziarz, Helena Elding Larsson, Markus Lundgren, Annelie Carlsson, Anna-Lena Nilsson, Malin Fex, Carina Törn, Daniel Agardh, Cheng-Ting Tsai, Åke Lernmark, Better Diabetes Diagnosis (BDD) Study Group

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	English
Article number	105144
Journal	EBioMedicine
Volume	104
Early online date	2024 May 8
DOIs	https://doi.org/10.1016/j.ebiom.2024.105144
Publication status	Published - 2024

Bibliographical note

Subject classification (UKÄ)

Endocrinology and Diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ebiom.2024.105144Licence: CC BY

BDD: Better Diabetes Diagnosis (BDD)
Carlsson, A. (PI), Lernmark, Å. (CoI), Elding Larsson, H. (CoI), Forsander, G. (Researcher), Ivarsson, S. (Researcher), Marcus, C. (Researcher), Ludvigsson, J. (CoI), Persson, M. (Researcher), Åkesson, K. (Researcher), Pundziute Lyckå, A. (Researcher), Palmkvist, E. (Researcher) & Hedlund, E. (Researcher)
Diabetesfonden - Stiftelsen Svenska Diabetesförbundets Forskningsfond, Swedish Child Diabetes Foundation
2005/05/01 → …
Project: Research

Cite this

Lind, A., Freyhult, E., de Jesus Cortez, F., Ramelius, A., Bennet, R., Robinson, P. V., Seftel, D., Gebhart, D., Tandel, D., Maziarz, M., Larsson, H. E., Lundgren, M., Carlsson, A., Nilsson, A.-L., Fex, M., Törn, C., Agardh, D., Tsai, C.-T., Lernmark, Å., & Better Diabetes Diagnosis (BDD) Study Group (2024). Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays. EBioMedicine, 104, Article 105144. https://doi.org/10.1016/j.ebiom.2024.105144

@article{c78498563b1c464f9909280569220d02,

title = "Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays",

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 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 {\"O}KS, Capital Region of Denmark, Region Sk{\aa}ne and the Novo Nordisk Foundation.",

author = "Alexander Lind and Eva Freyhult and {de Jesus Cortez}, Felipe and Anita Ramelius and Rasmus Bennet and Robinson, {Peter V} and David Seftel and David Gebhart and Devangkumar Tandel and Marlena Maziarz and Larsson, {Helena Elding} and Markus Lundgren and Annelie Carlsson and Anna-Lena Nilsson and Malin Fex and Carina T{\"o}rn and Daniel Agardh and Cheng-Ting Tsai and {\AA}ke Lernmark and {Better Diabetes Diagnosis (BDD) Study Group}",

year = "2024",

doi = "10.1016/j.ebiom.2024.105144",

language = "English",

volume = "104",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier",

}

Lind, A, Freyhult, E, de Jesus Cortez, F, Ramelius, A, Bennet, R, Robinson, PV, Seftel, D, Gebhart, D, Tandel, D, Maziarz, M , Larsson, HE , Lundgren, M , Carlsson, A, Nilsson, A-L, Fex, M , Törn, C , Agardh, D, Tsai, C-T, Lernmark, Å & Better Diabetes Diagnosis (BDD) Study Group 2024, 'Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays', EBioMedicine, vol. 104, 105144. https://doi.org/10.1016/j.ebiom.2024.105144

TY - JOUR

T1 - Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays

AU - Lind, Alexander

AU - Freyhult, Eva

AU - de Jesus Cortez, Felipe

AU - Ramelius, Anita

AU - Bennet, Rasmus

AU - Robinson, Peter V

AU - Seftel, David

AU - Gebhart, David

AU - Tandel, Devangkumar

AU - Maziarz, Marlena

AU - Larsson, Helena Elding

AU - Lundgren, Markus

AU - Carlsson, Annelie

AU - Nilsson, Anna-Lena

AU - Fex, Malin

AU - Törn, Carina

AU - Agardh, Daniel

AU - Tsai, Cheng-Ting

AU - Lernmark, Åke

AU - Better Diabetes Diagnosis (BDD) Study Group

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1016/j.ebiom.2024.105144

DO - 10.1016/j.ebiom.2024.105144

M3 - Article

C2 - 38723553

SN - 2352-3964

VL - 104

JO - EBioMedicine

JF - EBioMedicine

M1 - 105144

ER -

Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays

Abstract

Bibliographical note

Subject classification (UKÄ)

UN SDGs

Access to Document

Fingerprint

Projects

BDD: Better Diabetes Diagnosis (BDD)

Cite this