In another blog, we talked about genes and SNP and how they can affect Type 1 diabetes. In this part, we will look at autoantibodies. Autoantibodies are the current favourite target for Type 1 research, and some results are coming out showing that you can at least delay Type 1 if you target autoantibodies. We are all hoping that delay will last a lifetime.
So, what are autoantibodies? Essentially they are proteins that work with the immune system. All antibodies are generated to recognise Antigens, the structures, usually proteins of foreign tissue ( virus, bacteria) that flag them up as ‘foreign.’ Antibodies attach to these antigens and work with other parts of the immune system to render them harmless.
There are antibodies, and then there are autoantibodies. Autoantibodies recognise actual body tissues as foreign to the body and attack them instead. Over time the tissue becomes damaged or destroyed. It is thought that these autoantibodies are intended to neutralise an infectious agent or proteins that leak from the gut ( more later), but the shape of the antibody also fits human tissue.
Several autoantibodies are recognised in Type 1 diabetes. Some of these are routinely measured to assess diabetes risk or to clarify diagnosis where there is some doubt as to the type of diabetes a person has. Antibodies have been found to many parts of the insulin production and release tissues.
People can have more than one autoantibody. The antibody names are, Islet Cell Autoantibodies, (ICA), Insulin Autoantibodies (IAA), Glutamic Acid Decarboxylase Autoantibodies, GAD. Two types are known, but GAD 65 is associated with type1 diabetes. Protein Tyrosine Phosphatase Autoantibodies (ICA 2, ICA 512), and finally Zinc transporter eight autoantibodies(ZnT8). One thing to note here. I can get my head around Islet cell autoantibodies and Insulin autoantibodies. These directly destroy the ability to produce insulin. But GAD, ICA, and ZnT8? These are more involved in the processes that release insulin. GAD, glutamic acid decarboxylase, is an enzyme that is present throughout the whole body. So why it concentrates in the pancreas, I don’t know. When I look at a problem like this, it is useful to wonder why antibodies behave in this way. Why on earth is the body attacking the pancreas and sending the GAD autoantibodies there in high numbers, and not elsewhere? What is the immune system aiming at? Are the autoantibodies the fire alarm, or are they the actual fire?
To confuse matters, some people with autoantibodies will never get Type 1 diabetes. It seems to be the number of different antibodies present that is thought to be a better predictor of whether or not you will get Type 1 diabetes. Some laboratories have found that one autoantibody will appear first, and others often appear in a particular sequence over time.
And the complexity doesn’t end there. People with Type 1 diabetes in neighbouring countries, for example, Sweden and Lithuania, have different types of autoantibody. And there’s more, some children have developed Type 1 diabetes with no antibodies whatsoever—head-scratching time. I need a lie-down.
Welcome back. Let’s move on to inflammation.
What autoantibodies do is to work with the immune system to destroy pancreatic tissue that makes insulin. In the process of doing this, something called inflammation happens. Inflammation is nearly always associated with conditions where the body is trying to repair itself. A swollen knee after a fall is an excellent example of inflammation. So is tonsillitis. It is thought of as bad, but we should think of it as nothing more than the correct response to the condition. The body is recognising foreign
tissue and destroying it. When we have vaccinations, we are enabling our bodies to produce antibodies safely by injecting harmless proteins from viruses. The immune system will generate antibodies to these ‘foreign’ viral proteins. If the real virus then tries to attack us, for example, flu, it cannot get a foothold in the body because there are antibodies already waiting to neutralise it.
We can measure many proteins that are involved in generating an inflammatory response. There are many, and a growing number as we discover more. Also, we can look at specific types of immune cells called lymphocytes. These are specialised white blood cells ( leukocytes) and have great names such as killer T cells, helper T cells, and these give a clue to their actions. The ‘T’ is one type of lymphocyte or immune cell that has a different function to a ‘B’ lymphocyte. They are usually thought of as representing two different parts of the immune system. Imagine the surprise then when a type of lymphocyte was discovered called an X lymphocyte that can adapt to become either T or B. You might remember that we talked about genetic susceptibility in a previous blog. Well, it turns out that if you have a susceptible gene HLA-DQ8, you are more likely to generate a population of X lymphocytes that are hostile to insulin-producing cells. Drugs are targeted against lymphocytes. The drugs ending in -umab and -cept are used in a lot of inflammatory conditions, and they are being introduced into Type 1 trials.
And finally, after all of that process of recognising its own tissue as unwelcome, producing antibodies against it, and modifying the immune cells to attack it, there are the cytokines. Cyto means cell, kine? Anyone? Think of it as a protein that is produced by immune cells to enable communication between cells at a local level. You might have heard of interferon, tumor necrosis factor (TNF), and interleukins. ( probably not). In the process of autoimmune diseases, some interleukins, predominate in Type 1 diabetes, IL, 1,3, and 6.
So there you have it. Look up other blogs on the causes of Type 1 diabetes.