Abstract |
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.
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Authors | Helena Elding Larsson, Ida Jönsson, Ake Lernmark, Sten Ivarsson, Jared R Radtke, Christiane S Hampe, Diabetes Prediction in Skåne (DiPiS), Type 1 Diabetes Trial Network |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 6
Pg. e65173
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23785410
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Anti-Idiotypic
- Autoantibodies
- Glutamate Decarboxylase
- glutamate decarboxylase 2
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Topics |
- Adolescent
- Adult
- Antibodies, Anti-Idiotypic
(blood, immunology)
- Autoantibodies
(blood, immunology)
- Child
- Child, Preschool
- Cohort Studies
- Diabetes Mellitus, Type 1
(blood, immunology)
- Disease Progression
- Follow-Up Studies
- Glutamate Decarboxylase
(immunology)
- Humans
- Middle Aged
- Young Adult
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