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  1. Article
  2. Source: Campus Sanofi
  3. Jun 19, 2025

The role of antibodies and autoantibodies in autoimmune type 1 diabetes

Author: Sanofi

Editorial Team

B cells produce autoantibodies against pancreatic islet cells months and even up to years before the onset of clinically relevant symptoms of autoimmune type 1 diabetes (autoimmune T1D), providing an opportunity for early detection and potential prevention of autoimmune T1D onset.1-2 These type 1 diabetes (T1D) autoantibodies serve as important biomarkers for the development and progression of autoimmune T1D.1
What antibodies cause autoimmune T1D?Glutamic acid decarboxylase (GAD)Islet cell autoantibodies (ICA)Insulin (IAA)Protein tyrosine phosphatase (IA-2A)Zinc transporter (ZnT8)Which autoantibodies indicate disease progression?How can antibodies be used in autoimmune T1D detection and management?

What antibodies cause autoimmune T1D?

In autoimmune T1D, immune cells target and destroy the insulin-producing pancreatic beta-cells.3 This mechanism occurs in 4 distinct stages.2 
B cells produce antibodies that play a crucial role in the body’s defense mechanism against pathogens.4 In autoimmune T1D, this process is dysregulated, and the B cells secrete autoantibodies that bind to self-antigens.5 

Our understanding of the complex pathophysiology of autoimmune T1D is still evolving, however, several autoantibodies involved in autoimmune T1D have been identified.
The autoantibodies for autoimmune T1D include:1,2,6

  • Glutamic acid decarboxylase (GADA) autoantibodies
  • Islet cell autoantibodies (ICA)
  • Insulinoma-associated-2 autoantibodies (IA-2A)
  • Insulin autoantibodies (IAA)
  • Zinc transporter 8 autoantibodies (ZnT8A)

Antibody

Target Localization & Function

Detection in patients with autoimmune T1D

Glutamic acid decarboxylase (GAD) autoantibodies

GAD is found on synaptic-like vesicles in beta-cells. GAD antibodies can also be detected in other diseases, such as stiff person syndrome.7

GAD autoantibodies account for 65-74% of anti-islet autoantibodies.8

Islet cell autoantibodies (ICA)

The target proteins of this autoantibody are found on insulin secretory granule membranes, where they regulate the biogenesis and signaling of vesicles.7

ICA autoantibodies can be detected in 70-80% of patients newly diagnosed with autoimmune T1D.6

Insulinoma-associated-2 autoantibodies (IA-2A)

This autoantibody’s target is a transmembrane protein expressed on secretory granules within beta-cells.9 The function of the protein is unknown.1

This antibody emerges directly before the first symptoms of autoimmune T1D emerge and can be detected in 32-75% of newly diagnosed patients.7,10

Insulin autoantibodies (IAA)

IAA target endogenous insulin, whereas anti-insulin antibodies in autoimmune T1D target exogenously administered insulin.7

IAA or GAD autoantibodies are often detected first in the course of the disease.9 IAA is detected in 50-60% of pediatric patients and decreases with the progression of age.10

Zinc transporter 8 autoantibodies (ZnT8A)

The target of this autoantibody regulates zinc transport in secretory vesicles and is localized on beta cells.7,11

This antibody is detected directly before the first symptoms of autoimmune T1D emerge.7 ZnT8A can be detected in approximately 60% of patients.6

Which autoantibodies indicate disease progression?

The number of autoantibodies is thought to be correlated with the risk of disease progression, making them valuable markers and offer the possibility of preventing the clinical onset of T1D.2,12-13 Once autoantibodies are detected, the progression is faster in children than adults.14-15 

In children with no detectable autoantibodies, the diabetes risk by 15 years of age is 0.4%.15 The progression to autoimmune T1D is also rare in individuals with only 1 detectable autoantibody.16

In contrast, individuals with 2 or more detectable autoantibodies have a 70% risk of developing autoimmune T1D in the next 10 years and 100% risk over their lifetime.12

The first autoantibody that appears is often IAA, but in some populations, other autoantibodies are detected first.13 In particular, different age cohorts have a distinct autoantibody associated with the highest risk for autoimmune T1D.9 For instance, ZnT8A is linked to a higher risk in a subset of the older population.9

How can antibodies be used in autoimmune T1D detection and management?

Autoantibodies are increasingly important in diagnosing and screening patients with autoimmune T1D.1

Autoantibody screening of high-risk autoimmune T1D patients can be used to predict clinical stage autoimmune T1D before the onset of symptoms and allow early clinical interventions to prevent complications.17 Individuals with positive autoimmune T1D autoantibodies should be monitored over time.18

What are monoclonal antibody therapies for autoimmune T1D?

Monoclonal antibody therapies are used to prevent or delay autoimmune T1D by suppressing T cell stimulation and activity, thereby reducing the autoimmune response against pancreatic beta cells and helping to prevent the natural progression of the disease.11

There are different types of monoclonal antibodies; each type targets a distinct immune pathway.11,19

Learn more about using autoantibodies for screening of autoimmune T1D

References
  1. Katsarou A, Gudbjörnsdottir S, Rawshani A, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers. 2017;3:17016. doi:10.1038/nrdp.2017.16.
  2. Al-Mulla F, Alhomaidah D, Abu-Farha M, et al. Early autoantibody screening for type 1 diabetes: a Kuwaiti perspective on the advantages of multiplexing chemiluminescent assays. Front Immunol. 2023;14:1273476. doi:10.3389/fimmu.2023.1273476.
  3. Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964-1974. doi:10.2337/dc15-1419.
  4. Lee DSW, Rojas OL, Gommerman JL. B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat Rev Drug Discov. 2021;20(3):179-199. doi:10.1038/s41573-020-00092-2.
  5. Ma H, Murphy C, Loscher CE, O'Kennedy R. Autoantibodies - enemies, and/or potential allies?. Front Immunol. 2022;13:953726. doi:10.3389/fimmu.2022.953726.
  6. Winter WE, Pittman DL, Jialal I. Practical Clinical Applications of Islet Autoantibody Testing in Type 1 Diabetes. J Appl Lab Med. 2022;7(1):197-205. doi:10.1093/jalm/jfab113.
  7. Kawasaki E. Anti-Islet Autoantibodies in Type 1 Diabetes. Int J Mol Sci. 2023;24(12):10012. doi:10.3390/ijms241210012.
  8. Sims EK, Besser REJ, Dayan C, et al. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes. 2022;71(4):610-623. doi:10.2337/dbi20-0054.
  9. So M, Speake C, Steck AK, et al. Advances in Type 1 Diabetes Prediction Using Islet Autoantibodies: Beyond a Simple Count. Endocr Rev. 2021;42(5):584-604. doi:10.1210/endrev/bnab013.
  10. Pihoker C, Gilliam LK, Hampe CS, Lernmark A. Autoantibodies in diabetes. Diabetes. 2005;54 Suppl 2:S52-S61. doi:10.2337/diabetes.54.suppl_2.s52.
  11. Herold KC, Delong T, Perdigoto AL, Biru N, Brusko TM, Walker LSK. The immunology of type 1 diabetes. Nat Rev Immunol. 2024;24(6):435-451. doi:10.1038/s41577-023-00985-4.
  12. Simmons KM, Sims EK. Screening and Prevention of Type 1 Diabetes: Where Are We?. J Clin Endocrinol Metab. 2023;108(12):3067-3079. doi:10.1210/clinem/dgad328.
  13. Jia X, Yu L. Understanding Islet Autoantibodies in Prediction of Type 1 Diabetes. J Endocr Soc. 2024;8(1):bvad160. doi:10.1210/jendso/bvad160.
  14. Felton JL, Redondo MJ, Oram RA, et al. Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review. Commun Med (Lond). 2024;4(1):66.doi:10.1038/s43856-024-00478-y.
  15. Ziegler AG, Rewers M, Simell O, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013;309(23):2473-2479. doi:10.1001/jama.2013.6285.
  16. DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet. 2018;391(10138):2449-2462. doi:10.1016/S0140-6736(18)31320-5.
  17. Moore DJ, Leibel NI, Polonsky W, Rodriguez H. Recommendations for Screening and Monitoring the Stages of Type 1 Diabetes in the Immune Therapy Era. Int J Gen Med. 2024;17:3003-3014. doi:10.2147/IJGM.S438009.
  18. Phillip M, Achenbach P, Addala A, et al. Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetologia. 2024;67(9):1731-1759. doi:10.1007/s00125-024-06205-5.
  19. Ke Q, Kroger CJ, Clark M, Tisch RM. Evolving Antibody Therapies for the Treatment of Type 1 Diabetes. Front Immunol. 2021;11:624568. doi:10.3389/fimmu.2020.624568.

MAT-GLB-2502134-1.0-05/2025  

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