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Electrochemiluminescence Assays for Human Islet Autoantibodies
Published on: March 23, 2018
Autoantibodies against mitochondrial glycerophosphate dehydrogenase in patients with IDDM
M E Fabregat1, R Gasa, C Rodriguez
1Endocrinology Unit, Hospital Clinic, Barcelona, Spain.
Abstract:
The mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase (mGDH) plays a key role in the recognition of D-glucose as a stimulus for insulin release from the pancreatic islet B-cell. This study reveals that autoantibodies against this enzyme are not uncommonly found in patients with insulin-dependent diabetes mellitus (IDDM) examined at the onset of the disease. Antibodies reacting with a recombinant mGDH fragment product were observed in the serum of four out of 15 type-1 diabetics, but in none of 15 control subjects. The serum of patients positive for the recombinant mGDH fragment also recognized native mGDH in a rat testis extract, provided that the enzymatic protein was first exposed to an anti-mGDH rabbit serum. Antibodies against mGDH were also found in four out 12 patients with autoimmune thyroiditis. These findings reveal that a mitochondrial enzyme, that represents an essential component of the islet B-cell glucose-sensing device, may act as an antigenic determinant in patients with IDDM or other autoimmune diseases.
Insights
Autoantibodies against the mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase (mGDH) are present in type-1 diabetes patients. This enzyme is crucial for insulin release and may be an autoimmune target in diabetes and thyroiditis.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- The mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase (mGDH) is vital for glucose recognition in pancreatic islet B-cells, stimulating insulin release.
- Autoimmune diseases, including type 1 diabetes (T1D) and autoimmune thyroiditis, involve the immune system mistakenly attacking the body's own tissues.
Purpose of the Study:
- To investigate the presence and significance of autoantibodies targeting mGDH in patients with insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroiditis.
- To determine if mGDH can serve as an autoantigen in autoimmune conditions affecting glucose metabolism and insulin secretion.
Main Methods:
- Detection of autoantibodies against a recombinant mGDH fragment in the serum of T1D patients and healthy controls using immunoassays.
- Validation of antibody reactivity against native mGDH in rat testis extracts.
- Screening of patients with autoimmune thyroiditis for mGDH autoantibodies.
Main Results:
- Autoantibodies against mGDH were found in 4 out of 15 T1D patients at disease onset, but in none of the 15 control subjects.
- Antibodies from T1D patients recognized both recombinant and native mGDH.
- Antibodies against mGDH were also identified in 4 out of 12 patients with autoimmune thyroiditis.
Conclusions:
- The mitochondrial enzyme mGDH, a key component of the pancreatic B-cell glucose-sensing mechanism, can be an antigenic determinant in T1D.
- mGDH autoantibodies are present in a subset of T1D patients and individuals with autoimmune thyroiditis, suggesting a potential role in these autoimmune diseases.
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