A new test to identify cases of type 1 diabetes may soon be available thanks to technological advances.
The technology has been developed by Antigen Express, the wholly-owned subsidiary of NASDAQ-listed oral insulin delivery company Generex Biotechnology.
Currently, Type I diabetes can only be diagnosed by the presence of antibodies when the disease is already well underway.
Investigators were aware of Antigen Express technology whereby antigenic peptides linked to the "Ii-key" fragment of the MHC class II associated invariant chain enhances the presentation of those antigenic peptides.
Ii-Key/peptide 'hybrids' are able to bind directly to MHC class II molecules on the test cell's surface, thus obviating the need for antigen internalization within cells.
Earlier studies indicated that chemically linking the antigenic peptide to Ii-key through a flexible chemical linking agent could improve recognition of antigens, and may lead to a rapid, reliable assay for individuals with, or at risk for, Type-1 diabetes.
The antigen used in the study was GAD65, a protein that frequently triggers the autoimmune response in some diabetics. Researchers linked an antigenic peptide derived from GAD65 to the Ii-Key fragment, which is known to enhance presentation and binding of antigenic peptides directly to MHC Class II receptors on the cell surface.
In the study, researchers isolated peripheral blood mononuclear cells from thirteen patients with Type-1 diabetes, and 17 healthy subjects matched for age. Cells were cultured with either intact GAD65 or GAD65 peptides linked to Ii-Key, then analyzed for release of two cytokines associated with T cell activation: interferon gamma and interleukin-10. Cells from patients with Type I diabetes demonstrated a distinct profile of cytokine production compared to cells from healthy volunteers.
It was found that the interferon response to whole GAD65 was significantly greater in diabetic subjects compared to controls, but there was no difference in interleukin-10 responses between the groups. Type-1 diabetics also showed a similarly significant increase in interferon response to GAD65 Ii-Key peptides.
"The results show that Ii-Key/GAD65 hybrids produce a similar response from T cells as does the GAD65 protein. The cytokine expression profile we observe is helpful from a diagnostic perspective and gives hope that Ii-Key/GAD65 hybrids may have utility as agents to suppress autoimmunity," said Prof. David Leslie of the Department of Diabetes and Metabolism, St. Bartholomew's Hospital, London, U.K. and Antigen Express collaborator.
T cell reactivity to GAD65 is of particular interest in individuals who develop diabetes later in life, as this helps to differentiate them from the more common Type-2 diabetes.
As treatment and maintenance differ considerably for the two diseases, a validated diagnostic based on GAD65 could put those patients on the right treatment regimen earlier. A test based on ~ might also be useful in monitoring treatments of clinical-stage diabetes medications.
It could also help identify patients at high risk for developing Type-1 diabetes later in life, or who are at the disease's earliest stages.
This study will be presented at the American Diabetes Association's 68th Scientific Sessions meeting at the Moscone Convention Center in San Francisco.