Islet Autoantibody Standardization Program:  interlaboratory comparison of insulin autoantibody assay performance in 2018 and 2020 workshops

Ilaria Marzinotto; David Pittman; Alistair J K Williams; Anna E Long; Peter Achenbach; Schlosser Michael; Beena Akolkar; William Winter; Vito Lampasona

doi:10.1007/s00125-023-05877-9

Islet Autoantibody Standardization Program: interlaboratory comparison of insulin autoantibody assay performance in 2018 and 2020 workshops

Ilaria Marzinotto
, David Pittman
, Alistair J K Williams
, Anna E Long
, Peter Achenbach^*
, Schlosser Michael
, Beena Akolkar
, William Winter
, Vito Lampasona^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

58 Citations (Scopus)

Abstract

Aims/hypothesis
The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring autoantibodies in type 1 diabetes and the concordance of results across laboratories. IASP organises international workshops distributing anonymised serum samples to participating laboratories and centralises the collection and analysis of results. In this report, we describe the results of assays measuring IAA submitted to the IASP 2018 and 2020 workshops.

Methods
The IASP distributed uniquely coded sera from individuals with new-onset type 1 diabetes, multiple islet autoantibody-positive individuals, and diabetes-free blood donors in both 2018 and 2020. Serial dilutions of the anti-insulin mouse monoclonal antibody HUI-018 were also included. Sensitivity, specificity, area under the receiver operating characteristic curve (ROC-AUC), partial ROC-AUC at 95% specificity (pAUC95) and concordance of qualitative/quantitative results were compared across assays.

Results
Results from 45 IAA assays of seven different formats and from 37 IAA assays of six different formats were submitted to the IASP in 2018 and 2020, respectively. The median ROC-AUC was 0.736 (IQR 0.617–0.803) and 0.790 (IQR 0.730–0.836), while the median pAUC95 was 0.016 (IQR 0.004–0.021) and 0.023 (IQR 0.014–0.026) in the 2018 and 2020 workshops, respectively. Assays largely differed in AUC (IASP 2018 range 0.232–0.874; IASP 2020 range 0.379–0.924) and pAUC95 (IASP 2018 and IASP 2020 range 0–0.032).

Conclusions/interpretation
Assay formats submitted to this study showed heterogeneous performance. Despite the high variability across laboratories, the in-house radiobinding assay (RBA) remains the gold standard for IAA measurement. However, novel non-radioactive IAA immunoassays showed a good performance and, if further improved, might be considered valid alternatives to RBAs.

Original language	English
Pages (from-to)	897–912
Number of pages	16
Journal	Diabetologia
Volume	66
Issue number	5
Early online date	10 Feb 2023
DOIs	https://doi.org/10.1007/s00125-023-05877-9
Publication status	Published - 1 May 2023

Bibliographical note

Funding Information:
The Islet Autoantibody Standardization Program (IASP) has superseded the DASP in promoting the continuous improvement of type 1 diabetes autoantibody assays and disseminating empirically tested best-practice protocols, state-of-the-art reagents and serum standards []. The IASP is a collaborative effort supported by the Immunology of Diabetes Society (IDS) and the US NIH, which is run by the University of Florida Pathology Laboratories, Endocrine Autoantibody Laboratory and coordinated by an IDS nominated committee. The IASP pursues its goals through the establishment of a periodic interlaboratory comparison of type 1 diabetes-associated autoantibody measurements, aimed at providing an unbiased assessment of assay performance and improving the concordance of results across laboratories around the world. In IASP workshops the participating laboratories test type 1 diabetes autoantibodies in anonymised type 1 diabetes patient, ‘at-risk’ person, and control serum samples. An unbiased comparison of assay performance is provided through the centralised collection and analysis of results by the IASP committee.

Funding Information:
Open Access funding enabled and organized by Projekt DEAL. The authors acknowledge the support received by the IASP study through a TEDDY [] grant administered at the University of South Florida (Tampa, FL, USA) and by the Type 1 Diabetes TrialNet/IASP Ancillary studies arm [].

Funding Information:
We wish to thank all the people and the clinicians who contributed blood samples, without whose generosity and effort the IASP workshops and collaborative studies could not take place. We also wish to remember the precious contribution to both studies’ conception and data analysis of our friend and IASP committee member Alistair J. K. Williams, who passed away in 2020. PA is a member of the Editorial Board of Diabetologia. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. AJW, PA, MS, BA, DLP, WEW and VL contributed to the conception and design of the study. DLP and WEW organised and supervised sample preparation and distribution and data collection from participating laboratories. IM, DLP and VL contributed to the collection, preliminary analysis and interpretation of data. IM and VL drafted the initial manuscript. AJW, AEL, PA, MS, BA, DLP and WEW critically revised the data analysis and the manuscript. All authors approve of the publication. VL is the guarantor of the paper and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. S. N. Valdez, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina; K. Watson, Royal Melbourne Hospital, Melbourne, VIC, Australia; K. Verhaeghen, Uzbrussel Vub, Clinical Biology of Diabetes-Diabetes Research Center, Brussels, Belgium; V. Chen, Laboratory of Snibe, Shenzhen, China; J. Zhang, Shenzhen YHLO Biotech Co., Ltd, Shenzhen, China; Z. Zhou, G. Huang, Diabetes Center, Central South University, Changsha, China; R. Uibo, K. Reimand, University of Tartu, Department of Immunology, Tartu, Estonia; M. Knip, T. Härkönen, Children’s Hospital, Scientific Laboratory, University of Helsinki, Helsinki, Finland; R. Veijola, Department of Pediatrics, Diabetes Research Laboratory, University of Oulu, Oulu, Finland; L. Chatenoud, Laboratoire d’Immunologie Biologique-Hôpital Necker-Enfants Malades Paris, Paris, France; D. Mueller, Preclinical Approaches to Stem Cell Therapy/ Diabetes, Dresden, Germany; P. Achenbach, Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany; M. Schlosser, University Medical Center Greifswald, Karlsburg, Germany; V. Lampasona, Diabetes Research Institute, IRCCS Istituto Scientifico San Raffaele, Milano, Italy B. Almås, The Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; K. S. Opsion, Hormone Laboratory, Oslo University Hospital, Oslo, Norway; A. Ramelius, Diabetes And Celiac Disease Research Unit, Lund University, Malmö, Sweden; I. Johansson, Clinical & Experimental Research, Division of Pediatrics, Linköping, Sweden; M. R. Batstra, T. Cieremans, Reinier De Graaf Groep, Department of Medical Immunology, Delft, the Netherlands; S. Kostense, World Without Disease, Janssen, Leiden, the Netherlands; A. E. Long, Diabetes & Metabolism, Learning & Research, University of Bristol, Bristol, UK; A. Mathew, Meso Scale Diagnostics, LLC., Rockville, MD, USA; C. Hampe, University of Washington, Seattle, WA, USA; C. Lu, Meso Scale Discovery, Gaithersburg, MD, USA; C. Mann, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA; L. Yu, Barbara Davis Center, Aurora, CO, USA; M. Mamula, L2 Diagnostics at Yale University, New Haven, CT, USA; P. Robinson, Enable Biosciences, INC, San Francisco, CA, USA; W. A. Hagopian, Pacific Northwest Diabetes Research Institute, Seattle, WA, USA.

Publisher Copyright:
© 2023, The Author(s).

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Cite this

@article{70ebf55b71a8422c9bcbb2ee57b89322,

title = "Islet Autoantibody Standardization Program: interlaboratory comparison of insulin autoantibody assay performance in 2018 and 2020 workshops",

abstract = "Aims/hypothesis The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring autoantibodies in type 1 diabetes and the concordance of results across laboratories. IASP organises international workshops distributing anonymised serum samples to participating laboratories and centralises the collection and analysis of results. In this report, we describe the results of assays measuring IAA submitted to the IASP 2018 and 2020 workshops. Methods The IASP distributed uniquely coded sera from individuals with new-onset type 1 diabetes, multiple islet autoantibody-positive individuals, and diabetes-free blood donors in both 2018 and 2020. Serial dilutions of the anti-insulin mouse monoclonal antibody HUI-018 were also included. Sensitivity, specificity, area under the receiver operating characteristic curve (ROC-AUC), partial ROC-AUC at 95\% specificity (pAUC95) and concordance of qualitative/quantitative results were compared across assays. Results Results from 45 IAA assays of seven different formats and from 37 IAA assays of six different formats were submitted to the IASP in 2018 and 2020, respectively. The median ROC-AUC was 0.736 (IQR 0.617–0.803) and 0.790 (IQR 0.730–0.836), while the median pAUC95 was 0.016 (IQR 0.004–0.021) and 0.023 (IQR 0.014–0.026) in the 2018 and 2020 workshops, respectively. Assays largely differed in AUC (IASP 2018 range 0.232–0.874; IASP 2020 range 0.379–0.924) and pAUC95 (IASP 2018 and IASP 2020 range 0–0.032). Conclusions/interpretation Assay formats submitted to this study showed heterogeneous performance. Despite the high variability across laboratories, the in-house radiobinding assay (RBA) remains the gold standard for IAA measurement. However, novel non-radioactive IAA immunoassays showed a good performance and, if further improved, might be considered valid alternatives to RBAs.",

author = "Ilaria Marzinotto and David Pittman and Williams, \{Alistair J K\} and Long, \{Anna E\} and Peter Achenbach and Schlosser Michael and Beena Akolkar and William Winter and Vito Lampasona",

note = "Funding Information: The Islet Autoantibody Standardization Program (IASP) has superseded the DASP in promoting the continuous improvement of type 1 diabetes autoantibody assays and disseminating empirically tested best-practice protocols, state-of-the-art reagents and serum standards []. The IASP is a collaborative effort supported by the Immunology of Diabetes Society (IDS) and the US NIH, which is run by the University of Florida Pathology Laboratories, Endocrine Autoantibody Laboratory and coordinated by an IDS nominated committee. The IASP pursues its goals through the establishment of a periodic interlaboratory comparison of type 1 diabetes-associated autoantibody measurements, aimed at providing an unbiased assessment of assay performance and improving the concordance of results across laboratories around the world. In IASP workshops the participating laboratories test type 1 diabetes autoantibodies in anonymised type 1 diabetes patient, {\textquoteleft}at-risk{\textquoteright} person, and control serum samples. An unbiased comparison of assay performance is provided through the centralised collection and analysis of results by the IASP committee. Funding Information: Open Access funding enabled and organized by Projekt DEAL. The authors acknowledge the support received by the IASP study through a TEDDY [] grant administered at the University of South Florida (Tampa, FL, USA) and by the Type 1 Diabetes TrialNet/IASP Ancillary studies arm []. Funding Information: We wish to thank all the people and the clinicians who contributed blood samples, without whose generosity and effort the IASP workshops and collaborative studies could not take place. We also wish to remember the precious contribution to both studies{\textquoteright} conception and data analysis of our friend and IASP committee member Alistair J. K. Williams, who passed away in 2020. PA is a member of the Editorial Board of Diabetologia. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. AJW, PA, MS, BA, DLP, WEW and VL contributed to the conception and design of the study. DLP and WEW organised and supervised sample preparation and distribution and data collection from participating laboratories. IM, DLP and VL contributed to the collection, preliminary analysis and interpretation of data. IM and VL drafted the initial manuscript. AJW, AEL, PA, MS, BA, DLP and WEW critically revised the data analysis and the manuscript. All authors approve of the publication. VL is the guarantor of the paper and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. S. N. Valdez, Facultad de Farmacia y Bioqu{\'i}mica, Universidad de Buenos Aires, Buenos Aires, Argentina; K. Watson, Royal Melbourne Hospital, Melbourne, VIC, Australia; K. Verhaeghen, Uzbrussel Vub, Clinical Biology of Diabetes-Diabetes Research Center, Brussels, Belgium; V. Chen, Laboratory of Snibe, Shenzhen, China; J. Zhang, Shenzhen YHLO Biotech Co., Ltd, Shenzhen, China; Z. Zhou, G. Huang, Diabetes Center, Central South University, Changsha, China; R. Uibo, K. Reimand, University of Tartu, Department of Immunology, Tartu, Estonia; M. Knip, T. H{\"a}rk{\"o}nen, Children{\textquoteright}s Hospital, Scientific Laboratory, University of Helsinki, Helsinki, Finland; R. Veijola, Department of Pediatrics, Diabetes Research Laboratory, University of Oulu, Oulu, Finland; L. Chatenoud, Laboratoire d{\textquoteright}Immunologie Biologique-H{\^o}pital Necker-Enfants Malades Paris, Paris, France; D. Mueller, Preclinical Approaches to Stem Cell Therapy/ Diabetes, Dresden, Germany; P. Achenbach, Institute of Diabetes Research, Helmholtz Zentrum M{\"u}nchen, Neuherberg, Germany; M. Schlosser, University Medical Center Greifswald, Karlsburg, Germany; V. Lampasona, Diabetes Research Institute, IRCCS Istituto Scientifico San Raffaele, Milano, Italy B. Alm{\aa}s, The Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; K. S. Opsion, Hormone Laboratory, Oslo University Hospital, Oslo, Norway; A. Ramelius, Diabetes And Celiac Disease Research Unit, Lund University, Malm{\"o}, Sweden; I. Johansson, Clinical \& Experimental Research, Division of Pediatrics, Link{\"o}ping, Sweden; M. R. Batstra, T. Cieremans, Reinier De Graaf Groep, Department of Medical Immunology, Delft, the Netherlands; S. Kostense, World Without Disease, Janssen, Leiden, the Netherlands; A. E. Long, Diabetes \& Metabolism, Learning \& Research, University of Bristol, Bristol, UK; A. Mathew, Meso Scale Diagnostics, LLC., Rockville, MD, USA; C. Hampe, University of Washington, Seattle, WA, USA; C. Lu, Meso Scale Discovery, Gaithersburg, MD, USA; C. Mann, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA; L. Yu, Barbara Davis Center, Aurora, CO, USA; M. Mamula, L2 Diagnostics at Yale University, New Haven, CT, USA; P. Robinson, Enable Biosciences, INC, San Francisco, CA, USA; W. A. Hagopian, Pacific Northwest Diabetes Research Institute, Seattle, WA, USA. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

day = "1",

doi = "10.1007/s00125-023-05877-9",

language = "English",

volume = "66",

pages = "897–912 ",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "5",

}

TY - JOUR

T1 - Islet Autoantibody Standardization Program

T2 - interlaboratory comparison of insulin autoantibody assay performance in 2018 and 2020 workshops

AU - Marzinotto, Ilaria

AU - Pittman, David

AU - Williams, Alistair J K

AU - Long, Anna E

AU - Achenbach, Peter

AU - Michael, Schlosser

AU - Akolkar, Beena

AU - Winter, William

AU - Lampasona, Vito

N1 - Funding Information: The Islet Autoantibody Standardization Program (IASP) has superseded the DASP in promoting the continuous improvement of type 1 diabetes autoantibody assays and disseminating empirically tested best-practice protocols, state-of-the-art reagents and serum standards []. The IASP is a collaborative effort supported by the Immunology of Diabetes Society (IDS) and the US NIH, which is run by the University of Florida Pathology Laboratories, Endocrine Autoantibody Laboratory and coordinated by an IDS nominated committee. The IASP pursues its goals through the establishment of a periodic interlaboratory comparison of type 1 diabetes-associated autoantibody measurements, aimed at providing an unbiased assessment of assay performance and improving the concordance of results across laboratories around the world. In IASP workshops the participating laboratories test type 1 diabetes autoantibodies in anonymised type 1 diabetes patient, ‘at-risk’ person, and control serum samples. An unbiased comparison of assay performance is provided through the centralised collection and analysis of results by the IASP committee. Funding Information: Open Access funding enabled and organized by Projekt DEAL. The authors acknowledge the support received by the IASP study through a TEDDY [] grant administered at the University of South Florida (Tampa, FL, USA) and by the Type 1 Diabetes TrialNet/IASP Ancillary studies arm []. Funding Information: We wish to thank all the people and the clinicians who contributed blood samples, without whose generosity and effort the IASP workshops and collaborative studies could not take place. We also wish to remember the precious contribution to both studies’ conception and data analysis of our friend and IASP committee member Alistair J. K. Williams, who passed away in 2020. PA is a member of the Editorial Board of Diabetologia. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. AJW, PA, MS, BA, DLP, WEW and VL contributed to the conception and design of the study. DLP and WEW organised and supervised sample preparation and distribution and data collection from participating laboratories. IM, DLP and VL contributed to the collection, preliminary analysis and interpretation of data. IM and VL drafted the initial manuscript. AJW, AEL, PA, MS, BA, DLP and WEW critically revised the data analysis and the manuscript. All authors approve of the publication. VL is the guarantor of the paper and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. S. N. Valdez, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina; K. Watson, Royal Melbourne Hospital, Melbourne, VIC, Australia; K. Verhaeghen, Uzbrussel Vub, Clinical Biology of Diabetes-Diabetes Research Center, Brussels, Belgium; V. Chen, Laboratory of Snibe, Shenzhen, China; J. Zhang, Shenzhen YHLO Biotech Co., Ltd, Shenzhen, China; Z. Zhou, G. Huang, Diabetes Center, Central South University, Changsha, China; R. Uibo, K. Reimand, University of Tartu, Department of Immunology, Tartu, Estonia; M. Knip, T. Härkönen, Children’s Hospital, Scientific Laboratory, University of Helsinki, Helsinki, Finland; R. Veijola, Department of Pediatrics, Diabetes Research Laboratory, University of Oulu, Oulu, Finland; L. Chatenoud, Laboratoire d’Immunologie Biologique-Hôpital Necker-Enfants Malades Paris, Paris, France; D. Mueller, Preclinical Approaches to Stem Cell Therapy/ Diabetes, Dresden, Germany; P. Achenbach, Institute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany; M. Schlosser, University Medical Center Greifswald, Karlsburg, Germany; V. Lampasona, Diabetes Research Institute, IRCCS Istituto Scientifico San Raffaele, Milano, Italy B. Almås, The Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; K. S. Opsion, Hormone Laboratory, Oslo University Hospital, Oslo, Norway; A. Ramelius, Diabetes And Celiac Disease Research Unit, Lund University, Malmö, Sweden; I. Johansson, Clinical & Experimental Research, Division of Pediatrics, Linköping, Sweden; M. R. Batstra, T. Cieremans, Reinier De Graaf Groep, Department of Medical Immunology, Delft, the Netherlands; S. Kostense, World Without Disease, Janssen, Leiden, the Netherlands; A. E. Long, Diabetes & Metabolism, Learning & Research, University of Bristol, Bristol, UK; A. Mathew, Meso Scale Diagnostics, LLC., Rockville, MD, USA; C. Hampe, University of Washington, Seattle, WA, USA; C. Lu, Meso Scale Discovery, Gaithersburg, MD, USA; C. Mann, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA; L. Yu, Barbara Davis Center, Aurora, CO, USA; M. Mamula, L2 Diagnostics at Yale University, New Haven, CT, USA; P. Robinson, Enable Biosciences, INC, San Francisco, CA, USA; W. A. Hagopian, Pacific Northwest Diabetes Research Institute, Seattle, WA, USA. Publisher Copyright: © 2023, The Author(s).

PY - 2023/5/1

Y1 - 2023/5/1

N2 - Aims/hypothesis The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring autoantibodies in type 1 diabetes and the concordance of results across laboratories. IASP organises international workshops distributing anonymised serum samples to participating laboratories and centralises the collection and analysis of results. In this report, we describe the results of assays measuring IAA submitted to the IASP 2018 and 2020 workshops. Methods The IASP distributed uniquely coded sera from individuals with new-onset type 1 diabetes, multiple islet autoantibody-positive individuals, and diabetes-free blood donors in both 2018 and 2020. Serial dilutions of the anti-insulin mouse monoclonal antibody HUI-018 were also included. Sensitivity, specificity, area under the receiver operating characteristic curve (ROC-AUC), partial ROC-AUC at 95% specificity (pAUC95) and concordance of qualitative/quantitative results were compared across assays. Results Results from 45 IAA assays of seven different formats and from 37 IAA assays of six different formats were submitted to the IASP in 2018 and 2020, respectively. The median ROC-AUC was 0.736 (IQR 0.617–0.803) and 0.790 (IQR 0.730–0.836), while the median pAUC95 was 0.016 (IQR 0.004–0.021) and 0.023 (IQR 0.014–0.026) in the 2018 and 2020 workshops, respectively. Assays largely differed in AUC (IASP 2018 range 0.232–0.874; IASP 2020 range 0.379–0.924) and pAUC95 (IASP 2018 and IASP 2020 range 0–0.032). Conclusions/interpretation Assay formats submitted to this study showed heterogeneous performance. Despite the high variability across laboratories, the in-house radiobinding assay (RBA) remains the gold standard for IAA measurement. However, novel non-radioactive IAA immunoassays showed a good performance and, if further improved, might be considered valid alternatives to RBAs.

AB - Aims/hypothesis The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring autoantibodies in type 1 diabetes and the concordance of results across laboratories. IASP organises international workshops distributing anonymised serum samples to participating laboratories and centralises the collection and analysis of results. In this report, we describe the results of assays measuring IAA submitted to the IASP 2018 and 2020 workshops. Methods The IASP distributed uniquely coded sera from individuals with new-onset type 1 diabetes, multiple islet autoantibody-positive individuals, and diabetes-free blood donors in both 2018 and 2020. Serial dilutions of the anti-insulin mouse monoclonal antibody HUI-018 were also included. Sensitivity, specificity, area under the receiver operating characteristic curve (ROC-AUC), partial ROC-AUC at 95% specificity (pAUC95) and concordance of qualitative/quantitative results were compared across assays. Results Results from 45 IAA assays of seven different formats and from 37 IAA assays of six different formats were submitted to the IASP in 2018 and 2020, respectively. The median ROC-AUC was 0.736 (IQR 0.617–0.803) and 0.790 (IQR 0.730–0.836), while the median pAUC95 was 0.016 (IQR 0.004–0.021) and 0.023 (IQR 0.014–0.026) in the 2018 and 2020 workshops, respectively. Assays largely differed in AUC (IASP 2018 range 0.232–0.874; IASP 2020 range 0.379–0.924) and pAUC95 (IASP 2018 and IASP 2020 range 0–0.032). Conclusions/interpretation Assay formats submitted to this study showed heterogeneous performance. Despite the high variability across laboratories, the in-house radiobinding assay (RBA) remains the gold standard for IAA measurement. However, novel non-radioactive IAA immunoassays showed a good performance and, if further improved, might be considered valid alternatives to RBAs.

U2 - 10.1007/s00125-023-05877-9

DO - 10.1007/s00125-023-05877-9

M3 - Article (Academic Journal)

C2 - 36759347

SN - 0012-186X

VL - 66

SP - 897

EP - 912

JO - Diabetologia

JF - Diabetologia

IS - 5

ER -