Description
The islets of Langerhans collectively constitute 1-2% of the total volume of the pancreas. Each islet is composed of at least four endocrine cell types, including: insulin-secreting beta cells; glucagon-secreting alpha cells; somatostatin-secreting delta cells; and pancreatic polypeptide-secreting cells. Circulating antibodies to islet cells of the pancreas occur in most patients with Type I (insulin-dependent, juvenile) diabetes mellitus. The standard method for the detection of these antibodies has been indirect IF. Islet cell antibodies, when detected by indirect IF, stain the cytoplasm of islet cells of the pancreas from humans, monkeys and rats. The antibodies belong to the IgG class, and their titres are rather low, i.e usually under 1:160.The true islet cell antigens are poorly characterised but several have been identified on cytoplasmic membranes and on the cell surface of islet cells. Some diabetes associated autoantibodies recognise specifically the β cells whilst others recognise more widely distributed antigens. One autoantigen commonly recognised early in diabetes is the widely distributed neuroendocrine protein, glutamate decarboxylase-termed GAD (see specific page). There are two forms of GAD GAD65 and GAD70. Both forms of GAD have been identified in the brain as well as the islet cells. Within the islet, GAD may have a role in the inhibition of somatostatin and glucagon secretion and proinsulin synthesis. Some sera from type one diabetes patients recognise both forms of GAD but isoform specific antibodies also exist.
Other target antigens include insulin itself, a 38kDa autoantigen from insulin secretory granules, the glucose transporter, carboxypeptidase H and Islet cell antigen 512 (ICA512). Anti-insulin autoantibodies are present in the sera of about 50% of newly diagnosed IDD patients. IAA are highly associated with ICA. ICA and IAA found together in a single person confers a much greater risk for IDD development than does either marker alone. IAA when found in absence of ICA has only a low predictive value for progression to IDD. IAA assays are seldom necessary since anti-islet cell and anti-GAD will detect almost all IDDM. Note that the assay for anti-insulin antibodies produced as a result of use of heterologous insulin is NOT the same as that used for autoantibody detection.
Indication
Detection of Type1 diabetes.
Interpretation
Anti-islet cell antibodies are present in 90% of patients with Type I insulin-dependent/juvenile diabetes particularly around the time of diagnosis. They tend to disappear later unless there is multi-endocrine disorder. They are also found less commonly in non-diabetic relatives. They can serve as early markers to identify anti-islet cell autoimmunity before the onset of clinical symptoms. Anti-GAD65 autoantibodies have been reported in up to 78% of IDDM sera compared with only 1.7% of the healthy control sera. The GAD autoantigen has also been implicated in the rare neurological disorder, Stiff Man Syndrome (SMS) in which most patients have autoantibodies to GAD. Some but not all of these patients (around 30%) also have diabetes. Anti-insulin autoantibodies are present in the sera of about 50% of newly diagnosed IDD patients. IAA are highly associated with ICA IAA add little diagnostically to the much more readily available ICA and anti-GAD assays. IAA when found in absence of ICA has only a low predictive value for progression to IDD.
Assay details
Various. See individual tests.
Reference range
See individual tests.
Assay range notes
See individual tests.
Turnaround time
See individual tests.
Analysing laboratory
North Cumbria