Immunological biomarkers for the development and progression of type 1 diabetes

  • Chantal Mathieu
  • Riitta Lahesmaa
  • Ezio Bonifacio
  • Peter Achenbach
  • Timothy Tree


Immune biomarkers of type 1 diabetes are many and diverse. Some of these, such as the autoantibodies, are well established but not discriminative enough to deal with the heterogeneity inherent to type 1 diabetes progression. As an alternative, high hopes are placed on T cell assays, which give insight into the cells that actually target the beta cell or play a crucial role in maintaining tolerance. These assays are approaching a level of robustness that may allow for solid conclusions on both disease progression and therapeutic efficacy of immune interventions. In addition, ‘omics’ approaches to biomarker discovery are rapidly progressing. The potential emergence of novel biomarkers creates a need for the introduction of bioinformatics and ‘big data’ analysis systems for the integration of the multitude of biomarker data that will be available, to translate these data into clinical tools. It is worth noting that it is unlikely that the same markers will apply to all individuals. Instead, individualised signatures of biomarkers, combining autoantibodies, T cell profiles and other biomarkers, will need to be used to classify at-risk patients into various categories, thus enabling personalised prediction, prevention and treatment approaches. To achieve this goal, the standardisation of assays for biomarker discovery, the integration of analyses and data from biomarker studies and, most importantly, the careful clinical characterisation of individuals providing samples for these studies are critical. Longitudinal sample-collection initiatives, like INNODIA, should lead to novel biomarker discovery, not only providing a better understanding of type 1 diabetes onset and progression, but also yielding biomarkers of therapeutic efficacy of interventions to prevent or arrest type 1 diabetes.


Autoantibodies Bioinformatics Biomarker Immune Review T cell assays Type 1 diabetes 



Forkhead box P3


Glutamic acid decarboxylase


Islet antigen-2


Immunology of Diabetes Society




Peripheral blood mononuclear cells


Effector T cells


Regulatory T cells


Zinc transporter-8



We thank C. Moyson (Department of Endocrinology, UZ Leuven, Leuven, Belgium) for editorial help.

Contribution statement

All authors were responsible for drafting the article and revising it critically for important intellectual content. All authors approved the version to be published.


Related work in the laboratories of all authors is funded by the Innovative Medicines Initiative 2 Joint Undertaking (IMI2-JU) under grant agreement no. 115797 INNODIA. This joint undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA, JDRF International and The Leona M. and Harry B. Helmsley Charitable Trust.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Chantal Mathieu
    • 1
  • Riitta Lahesmaa
    • 2
  • Ezio Bonifacio
    • 3
    • 4
    • 5
  • Peter Achenbach
    • 5
    • 6
  • Timothy Tree
    • 7
    • 8
  1. 1.Department of EndocrinologyUniversity Hospital Gasthuisberg, KU LeuvenLeuvenBelgium
  2. 2.Turku Centre for BiotechnologyUniversity of Turku and Åbo Akademi UniversityTurkuFinland
  3. 3.DFG Center for Regenerative Therapies Dresden, Faculty of MedicineTechnische Universität DresdenDresdenGermany
  4. 4.Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital Carl Gustav Carus, Medical FacultyTechnische Universität DresdenDresdenGermany
  5. 5.German Center for Diabetes Research (DZD)NeuherbergGermany
  6. 6.Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Diabetes ResearchMunich-NeuherbergGermany
  7. 7.Department of Immunobiology, School of Immunology & Microbial Sciences, King’s College LondonBorough Wing Guy’s HospitalLondonUK
  8. 8.NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust and King’s College LondonLondonUK

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