Autoantibody-Negative Type 1 Diabetes: A Neglected Subtype

Shivani K Patel; Cindy S Ma; Spiros Fourlanos; Jerry R Greenfield

doi:10.1016/j.tem.2021.02.001

Autoantibody-Negative Type 1 Diabetes: A Neglected Subtype

Trends Endocrinol Metab. 2021 May;32(5):295-305. doi: 10.1016/j.tem.2021.02.001. Epub 2021 Mar 9.

Authors

Shivani K Patel¹, Cindy S Ma², Spiros Fourlanos³, Jerry R Greenfield⁴

Affiliations

¹ Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia; Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
² St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia; Human Immune Disorders, Garvan Institute of Medical Research, Sydney, NSW, Australia.
³ Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
⁴ Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia; Department of Diabetes and Endocrinology, St. Vincent's Hospital, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia. Electronic address: j.greenfield@garvan.org.au.

PMID: 33712367
DOI: 10.1016/j.tem.2021.02.001

Abstract

Up to 15% of individuals with a clinical phenotype of type 1 diabetes (T1D) do not have evidence of seropositivity for pancreatic islet autoantibodies. On this basis, they are classified as nonimmune or idiopathic, and remain an understudied population, as they are excluded from T1D immunomodulatory trials. Our limited understanding of the disease aetiopathogenesis in autoantibody-negative T1D hinders our ability to improve diagnostic pathways and discover novel therapeutic agents; particularly as we progress towards an era of precision medicine. This review summarises the current understanding and challenges in studying autoantibody-negative T1D. We review the literature regarding T1D classification, and the role of autoimmunity and defects in the immunogenic pathway that may distinguish autoantibody-positive and -negative T1D.

Keywords: autoantibody-negative; autoimmune diabetes; characterisation; immunophenotype; type 1 diabetes.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Autoantibodies*
Autoimmunity
Diabetes Mellitus, Type 1* / immunology
Humans
Islets of Langerhans* / immunology

Substances

Autoantibodies