IA2

Type 1 diabetes, also known as insulin-dependent
diabetes mellitus (IDDM), results from a chronic
autoimmune destruction of the insulin-secreting
pancreatic beta cells, probably initiated by exposure
of genetically susceptible host to an environmental
agent. Autoimmune destruction of beta cells is
thought to be completely asymptomatic until 80 - 90%
of the cells are lost. This process may take years to
complete and may occur at any time. During the
preclinical phase, this autoimmune process is marked
by circulating autoantibodies to beta cell antigens.
These autoantibodies are present years before the
onset of type 1 diabetes and prior to clinical
symptoms. Early studies utilized the
immunofluorescence test for islet-cell antibodies
(ICA), which has been difficult to Calibratorize and is
now replaced by a combination of several
radioimmunoassays for antibodies against specific
beta cell antigens, such as insulin (IAA), glutamic acid
decarboxylase (GAD) and tyrosine phosphatase ICA
512 (IA2). IA2, a member of the protein tyrosine
phosphatases family is localized in the dense
granules of pancreatic beta cells and the second
defined recombinant islet cell antigen. IA2 shares
sequence identity with the islet cell antigen 512. The
higher frequency of antibodies to IA2 is explained by
the presence of autoantibodies directed to the COOH
terminus of IA2 which is lacking in the ICA512
molecule. IA2 autoantibodies are present in the
majority of individuals with new-onset type 1 diabetes
and in individuals in the pre-diabetic phase of the
disease. The appearance of autoantibodies to IA2
seems to be correlated with the rapid progression to
overt type 1 diabetes.
The combination of tests for GAD65 and IA2
autoantibodies is highly relevant for risk assessment
of type 1 diabetes in children and adolescence. The
screening for GAD65 and IA2 autoantibodies detect
more than 90 % of subjects at risk for type 1 diabetes
and may, therefore, possess the potential to replace
ICA technique.