t is probably a safe bet that everyone reading this knows at least one person who has diabetes. Diabetes is such a common disease in our culture, we hardly blink anymore when we find out that someone has it, as opposed to more ominous diseases like cancer, cardio-vascular disease or AIDS. Diabetes is the common name for Diabetes mellitus, but it is also a generalized term that combines two very different diseases that produce similar symptoms and effects. When we hear the word “diabetes”, most immediately think of the Type 2 version, the overweight and unhealthy, dietary disease that affects nearly 10% of all Americans and more than 300 million people worldwide. That’s not surprising, since Type 2 diabetes (T2DM) makes up approximately 90% of all diabetes cases. But there’s a huge difference between Type 2 and Type 1 diabetes (T1DM).
Whereas T2DM can be largely traced to poor nutritional and lifestyle choices, along with a smattering of genetic predispositions, which collectively gang up against the body’s insulin and prevent it from doing its job, rather like the fairy tale Cinderella’s step-mother and sisters preventing her from going to the ball. However, T1DM is actually an autoimmune disease in which the body’s immune system goes haywire and begins targeting the insulin-producing beta cells in the pancreas. Imagine how bad that infamous story would have been if Cinderella’s had been killed by her wicked step-mother immediately after her father died instead.
T1DM isn’t just insulin resistance, it’s the loss of most or all of the insulin in the body, due to the destruction of the cells that produce it. The end-effect looks identical to T2DM, which is why they are both commonly called the same thing, but where Type 2 can be possibly be reversed with proper diet and better exercise, Type 1 is a lifelong condition that has little to no chance of ever going away. Also, to date, T1DM cannot be prevented. While it’s known what happens, we still do not know why; whether it’s a simply genetic susceptibility or some kind of external trigger or some combination of the two or even something else that’s yet to be discovered.
However, scientists have noticed patterns of autoantibodies that have been able to predict the onset of T1DM. Autoantibodies for islet cells (also called islet of Langerhans), the cells responsible for producing the beta cells which monitor sugar levels and release insulin, for insulin, for glutamic acid decarboxylase (GAD65), for protein tyrosine phosphatase (IA-2) and for zinc transporter 8 (ZnT8) all account for some degree of T1DM onset. The more, different autoantibodies found, the higher the likelihood of eventually developing T1DM. The presence of these autoantibodies is sometimes called “latent autoimmune diabetes” and there are some doctors who believe that if these autoantibodies can be detected and suppressed early enough, then full onset T1DM might be preventable.
Since insulin autoantibodies (IAA) are usually the first to appear, they are an enticing target for scientists and it should be an easy and simple ELISA experiment, but IAAs are additionally bothersome in that they refuse to bind to human insulin which has been bound to an ELISA plate. Several other methods, such as RIA (radioimmunoassay) and ECL (electrochemiluminescence), have therefore been developed. But RIA depends on radiolabeled antigens, which are always a pain to deal with, and ECL requires high cost equipment and training and there have been reports of poor result correlation between labs. But what if there was a way to make that ELISA work after all? Well, a group from France, led by Nathalie Morel, think they’ve found a way.
Morel’s concept is called a Bridge-ELISA. Binding the IAA to a biotinylated insulin in one of its antigen-binding domain allowed for easy detection via a streptavidin-conjugated tracer, and the other of its antigen-binding domains was bound to a GC300 hapten to help bind to an ELISA plate coated with the anti-GC300 monoclonal antibody MC159. Ultimately, Morel’s group developed a process that is faster, simpler to use and more reliable than ECL, and was safer (since there is no radioactive components) than the traditional RIA method, although it was only about 80% as sensitive as RIA in detecting IAA’s in T1DM children. Because it utilizes the standard ELISA format, practically every protein lab in the world can do it and automate the process for large-scale, faster results. And when it comes to saving insulin producing beta cells and possibly preventing T1DM, every small step forward might help to save a life you know.
Kikkas I, Mallone R, Tubiana-Rufi N, Chevenne D, Carel JC, Creminon, C., Volland, H., Boitard, C. and Morel, N. (2013) A Simple and Fast Non-Radioactive Bridging Immunoassay for Insulin Autoantibodies. PLoS ONE 8(7): e69021. doi:10.1371/journal.pone.0069021
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