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Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets
Norio Kanatsuna1, Jalal Taneera, Fariba Vaziri-Sani
1From the Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Skåne University Hospital SUS, SE-205 02 Malmö, Sweden and.
The Journal of Biological Chemistry
|August 13, 2013
Summary
A novel autoantigen, INS-IGF2, containing insulin components, shows increased autoantibodies in type 1 diabetes patients. This finding challenges insulin
Area of Science:
- Immunology
- Endocrinology
- Genetics
Background:
- Insulin is a key autoantigen in islet autoimmunity and type 1 diabetes development.
- The insulin B-chain is hypothesized to be critical in insulin autoimmunity.
- INS-IGF2 is a fusion protein containing insulin B-chain and IGF2 components.
Purpose of the Study:
- To investigate the expression of INS-IGF2 in human pancreatic islets.
- To assess autoantibody levels against INS-IGF2 in children with type 1 diabetes and controls.
Main Methods:
- Quantitative analysis of INS-IGF2 expression in pancreatic islets from normal, type 2 diabetes, and high HbA1c donors.
- Measurement of INS-IGF2 autoantibody levels in newly diagnosed type 1 diabetes patients and healthy controls.
- Autoantibody reactivity assessment using displacement assays with cold insulin and INS-IGF2.
Main Results:
- INS-IGF2 is expressed in pancreatic beta cells, with higher levels in normal islets compared to type 2 diabetes or high HbA1c donors.
- Autoantibody levels against INS-IGF2 were significantly elevated in type 1 diabetes patients versus controls.
- A higher proportion of type 1 diabetes patients exhibited doubly reactive autoantibodies to both insulin and INS-IGF2.
Conclusions:
- INS-IGF2, containing critical insulin components, may function as an autoantigen in type 1 diabetes.
- Shared autoantibody-binding sites between INS-IGF2 and insulin complicate the understanding of insulin as the sole primary autoantigen.
- This suggests a more complex autoimmune response in type 1 diabetes involving novel autoantigens.
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