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Guidelines for standardizing T-cell cytometry assays to link biomarkers, mechanisms, and disease outcomes in type 1 diabetes

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Immunology of Diabetes Society T-Cell Cytometry Group, Jennie H.M. Yang, Kirsten A. Ward-Hartstonge, Daniel J. Perry, J. Lori Blanchfield, Amanda L. Posgai, Alice E. Wiedeman, Kirsten Diggins, Adeeb Rahman, Timothy I.M. Tree, Todd M. Brusko, Megan K. Levings, Eddie A. James, Sally C. Kent, Cate Speake, Dirk Homann, S. Alice Long

Original languageEnglish
Pages (from-to)372-388
Number of pages17
JournalEuropean Journal of Immunology
Volume52
Issue number3
Early online date28 Jan 2022
DOIs
Accepted/In press22 Dec 2021
E-pub ahead of print28 Jan 2022
Published4 Mar 2022

Bibliographical note

Funding Information: T.M.B. is supported by the National Institutes of Health (P01 AI042288, R01 DK106191, HIRN UC4 DK104194), and The Leona M. and Harry B. Helmsley Charitable Trust. D.H. and A.H.R are supported by Juvenile Diabetes Research Foundation Strategic Research Agreement JDRF 2‐SRA‐2018‐643‐M‐B and D.H. is supported by National Institutes of Health (NIH) grants U01DK123716, UC4DK116284, and P30DK02054141. E.A.J. is supported by grants from the JDRF (1‐SRA‐2017‐344‐S‐B and 2‐SRA‐2018‐551‐S‐B). S.C.K. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (UC4 DK116284) and S.C.K. is the George F. and Sybil H. Fuller Term Chair in Diabetes. M.K.L and K.A.W.‐H are supported by JDRF (3‐SRA‐2018‐629‐S‐B). K.A.W.‐H is supported by the JDRF (1‐PDF‐2019‐709‐A‐N), the Canadian Institutes of Health Research Canadian (CIHR), and the Association of Gastroenterology (CAG) (201711FGA‐398491‐294541). S.A.L is supported by a grant from the JDRF (3‐SRA‐2019‐792‐S‐B) and the National Institutes of Health (R01 AI141952). C.S. is supported by a grant from the JDRF (3‐SRA‐2019‐791‐S‐B). T.I.M.T. and J.H.M.Y. are supported by the T1DUK Immunotherapy Consortium funded by grants from Diabetes UK (Ref: 15/0005232 and 15/0005233) and from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Center award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115797 (INNODIA), which receives support from the European Union's Horizon 2020 research and innovation programme and “EFPIA,” “JDRF,” and “The Leona M. and Harry B. Helmsley Charitable Trust.” All authors are the guarantors of this work. Funding Information: We appreciate the Immunology of Diabetes Society T-Cell Workshop and the Immunology of Diabetes Society T-Cell Cytometry Group for fostering discussions that launched this manuscript. We thank Thinzar Myint (University of Florida) for aid with graphics. T.M.B. is supported by the National Institutes of Health (P01 AI042288, R01 DK106191, HIRN UC4 DK104194), and The Leona M. and Harry B. Helmsley Charitable Trust. D.H. and A.H.R are supported by Juvenile Diabetes Research Foundation Strategic Research Agreement JDRF 2-SRA-2018-643-M-B and D.H. is supported by National Institutes of Health (NIH) grants U01DK123716, UC4DK116284, and P30DK02054141. E.A.J. is supported by grants from the JDRF (1-SRA-2017-344-S-B and 2-SRA-2018-551-S-B). S.C.K. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (UC4 DK116284) and S.C.K. is the George F. and Sybil H. Fuller Term Chair in Diabetes. M.K.L and K.A.W.-H are supported by JDRF (3-SRA-2018-629-S-B). K.A.W.-H is supported by the JDRF (1-PDF-2019-709-A-N), the Canadian Institutes of Health Research Canadian (CIHR), and the Association of Gastroenterology (CAG) (201711FGA-398491-294541). S.A.L is supported by a grant from the JDRF (3-SRA-2019-792-S-B) and the National Institutes of Health (R01 AI141952). C.S. is supported by a grant from the JDRF (3-SRA-2019-791-S-B). T.I.M.T. and J.H.M.Y. are supported by the T1DUK Immunotherapy Consortium funded by grants from Diabetes UK (Ref: 15/0005232 and 15/0005233) and from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Center award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115797 (INNODIA), which receives support from the European Union's Horizon 2020 research and innovation programme and “EFPIA,” “JDRF,” and “The Leona M. and Harry B. Helmsley Charitable Trust.” All authors are the guarantors of this work. Publisher Copyright: © 2022 Wiley-VCH GmbH

King's Authors

Abstract

Cytometric immunophenotyping is a powerful tool to discover and implement T-cell biomarkers of type 1 diabetes (T1D) progression and response to clinical therapy. Although many discovery-based T-cell biomarkers have been described, to date, no such markers have been widely adopted in standard practice. The heterogeneous nature of T1D and lack of standardized assays and experimental design across studies is a major barrier to the broader adoption of T-cell immunophenotyping assays. There is an unmet need to harmonize the design of immunophenotyping assays, including those that measure antigen-agnostic cell populations, such that data collected from different clinical trial sites and T1D cohorts are comparable, yet account for cohort-specific features and different drug mechanisms of action. In these Guidelines, we aim to provide expert advice on how to unify aspects of study design and practice. We provide recommendations for defining cohorts, method implementation, as well as tools for data analysis and reporting by highlighting and building on selected successes. Harmonization of cytometry-based T-cell assays will allow researchers to better integrate findings across trials, ultimately enabling the identification and validation of biomarkers of disease progression and treatment response in T1D.

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