Research
Autoimmune diseases are due to destructive immune reactions which target specific proteins (auto antigens). Immune effector cells recognising specific auto antigens probably cause type 1 diabetes through destruction of insulin secreting cells and Stiff Man Syndrome (SMS) through impairment of nerve transmission. A combination of cellular and humoral immune changes are associated with disease development in both conditions and in both diseases the enzyme Glutamic Acid Decarboxylase-65 GAD65) is a major target auto antigen.
Preliminary studies demonstrated distinct immune responses to GAD between SMS and Type 1 diabetes. Diabetes develops in about half SMS patients and half identical twins of type 1 diabetes patients. we have the world’s largest collection of each disease. We aim to determine whether immune response to GAD in SMS patients and twin pairs with type I diabetes are: 1) disease—specific; and 2) associated with protection from diabetes. Differences between diabetic and non-diabetic cases will help understand the diseases and develop treatment based on modulating GAD reactivity
l.So far we have measured GAD and other antibodies on 10 of the referred patients. We have more samples to collect this will be done shortly. I am about to start sending out kits for the GP’s to take blood and send it to us. Our GAD assay is one of the best and we have samples sent to us from around the UK for measurement of GAD on both newly diagnosed diabetics and possible SMS patients. We are about to start measuring antibody isotypes on all the SMS patients and will ask for further sera to do this. We have a new and improved assay for this measurement. Preliminary studies suggest further differences in the isotype profile of GAD as well as other diabetic associated antibodies between SMS and type I diabetes.
2. The BNSU (British Neurological Surveillance Unit) have sent
out cards to all the neurologists in the UK in an attempt to identify the
incidence of SMS in the country. The neurologists are asked to report all
cases of SMS to the BNSU and they then inform us. We write to the neurologists
w ho give us brief details of the patients if they do not
wish to be involved or give us permission to contact the patients if they
are interested.
3. The BNSL are to Continue a further one year ascertainment. We will carry out cellular testing when funds are available. For this our nurse will visit all those who cannot travel to collect whole fresh blood.
4. We have started Phase 2 studies with injections of either GAD or Heat Shock protein in patients with diabetes and LADA (Latent Autoimmune Diabetes of Adults) in an attempt to prevent them going on to insulin by altering the adverse immune reaction. This could also hopefully be of help to SMS in the future and studies of the nerve and muscle function of these cases are underway.
We will obviously need considerable funds to continue this work and any contributions however great ( and the greater the better!!) or small will be appreciated.
Professor RDH Leslie
Professor of Diabetes and Autoimmunity