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Åke Lernmark

Principal investigator

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Decline in Titers of Anti-Idiotypic Antibodies Specific to Autoantibodies to GAD65 (GAD65Ab) Precedes Development of GAD65Ab and Type 1 Diabetes.

Author

  • Helena Larsson
  • Ida Jönsson
  • Åke Lernmark
  • Sten Ivarsson
  • Jared R Radtke
  • Christiane S Hampe

Summary, in English

The humoral Idiotypic Network consisting of antibodies and their anti-idiotypic antibodies (anti-Id) can be temporarily upset by antigen exposure. In the healthy immune response the original equilibrium is eventually restored through counter-regulatory mechanisms. In certain autoimmune diseases however, autoantibody levels exceed those of their respective anti-Id, indicating a permanent disturbance in the respective humoral Idiotypic Network. We investigated anti-Id directed to a major Type 1 diabetes (T1D)-associated autoantibody (GAD65Ab) in two independent cohorts during progression to disease. Samples taken from participants of the Natural History Study showed significantly lower anti-Id levels in individuals that later progressed to T1D compared to non-progressors (anti-Id antibody index of 0.06 vs. 0.08, respectively, p = 0.02). We also observed a significant inverse correlation between anti-Id levels and age at sampling, but only in progressors (p = 0.014). Finally, anti-Id levels in progressors showed a significant decline during progression as compared to longitudinal anti-Id levels in non-progressors (median rate of change: -0.0004 vs. +0.0004, respectively, p = 0.003), suggesting a loss of anti-Id during progression. Our analysis of the Diabetes Prediction in Skåne cohort showed that early in life (age 2) individuals at risk have anti-Id levels indistinguishable from those in healthy controls, indicating that low anti-Id levels are not an innate characteristic of the immune response in individuals at risk. Notably, anti-Id levels declined significantly in individuals that later developed GAD65Ab suggesting that the decline in anti-Id levels precedes the emergence of GAD65Ab (median rate of change: -0.005) compared to matched controls (median rate of change: +0.001) (p = 0.0016). We conclude that while anti-Id are present early in life, their levels decrease prior to the appearance of GAD65Ab and to the development of T1D.

Department/s

  • Paediatric Endocrinology
  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2013

Language

English

Publication/Series

PLoS ONE

Volume

8

Issue

6

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Paediatric Endocrinology
  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 1932-6203