Autoantibodies against mitochondrial glycerophosphate dehydrogenase in patients with IDDM.
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.
Fabregat
M E
ME
Endocrinology Unit, Hospital Clinic, Barcelona, Spain.
Gasa
R
R
Rodriguez
C
C
Novials
A
A
Gallart
T
T
Malaisse
W J
WJ
Gomis
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology*; D005260:Female; D005982:Glutathione Transferase / Q000276:immunology; D005993:Glycerolphosphate Dehydrogenase / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D011817:Rabbits / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D013737:Testis / Q000201:enzymology / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000201:enzymology / Q000276:immunology
D001323:Autoantibodies; D007106:Immune Sera; D011994:Recombinant Proteins; D005993:Glycerolphosphate Dehydrogenase; D005982:Glutathione Transferase