New antigen for type 1 diabetes confirmed
Scientists at the Research Center for Regenerative Therapies in Dresden, the Helmholtz Zentrum München and the German Center for Diabetes Research have identified four autoantigens that have recently been discovered to be associated with autoimmune diseases associated with the HLA genotype. For example, the HLA genotype plays a role in disease development of type 1 diabetes. Thus, HLA genes are known which increase or decrease the susceptibility to type 1 diabetes. Autoantibodies directed against these new antigens appear to be more prevalent in patients with certain genotypes shortly after the onset of type 1 diabetes.
In cooperation with the Dresden University of Technology and the Institute for Diabetes and Obesity at the Helmholtz Zentrum München, researchers from the Institute for Diabetes Research as partners in the German Center for Diabetes Research have tested new antigens for their association with type 1 diabetes. The scientists studied patients with type 1 diabetes shortly after onset of the disease for antibodies against three proteins involved in nuclear repair or transport processes - namely MLH1, NUP50 and PPIL2 - as well as antibodies to the translation initiation factor MTIF3, which is involved in the production of Proteins of mitochondria involved. The scientists wanted to gain some insight into how immunity, or, in contrast, increased susceptibility to autoimmune diseases arises.
Blood analysis revealed the following results: In patients, autoantibodies to the four new antigens were significantly more common than those in healthy controls. Patients with HLA DR3 genotype had more frequent antibodies to NUP50. If they had an HLA DR4 genotype, antibodies to MLH1 were found more frequently.
To date, the measurement of autoantibodies against four other antigens provides very reliable indications for the early detection of type 1 diabetes: they are antibodies against the endogenous hormone insulin, glutamate decarboxylase 65 (GAD65), tyrosine phosphatase (IA- 2) and the zinc transporter 8 (ZnT8). Since these antigens often initiate an autoimmune process that can later lead to type 1 diabetes, they serve as immune markers in early detection studies such as the Fr1da study or the NHS TrialNet study of the Institute for Diabetes Research at Helmholtz Zentrum München. Their detection indicates an asymptomatic early stage of type 1 diabetes.
However, autoantibodies to the newly discovered antigens will probably not be used in screening for type 1 diabetes, although they have been shown to be associated with it. "The newly discovered antigens are less important target targets for diabetes-specific autoantibodies because they only occur in subgroups of patients," said one of the first authors, Tanja Telieps.
Nonetheless, antigenicity may be of concern to affected patients, as study leader Professor Ezio Bonifacio notes: "The autoimmunity to individual proteins associated with the nucleus or mitochondria in a subgroup of patients may be indicative of systemic autoimmunity his. This would show for the first time that some patients with type 1 diabetes also show signs of systemic autoimmunity. This new finding may be important in elucidating the pathogenesis of type 1 diabetes."