Early Thymic Expression in Autoimmune Diseases
Research type
Research Study
Full title
Early Thymic Expression in Autoimmune Diseases
IRAS ID
145173
Contact name
Richard DG Leslie
Contact email
Sponsor organisation
Queen Mary University of London
Duration of Study in the UK
2 years, 11 months, 31 days
Research summary
Autoimmune diseases, such as type 1 diabetes (T1D), thyroiditis and multiple sclerosis, affect as much as 10% of the population with a major impact on morbidity and mortality. The co-occurrence of autoimmune diseases suggests a common pathophysiology that likely revolves around genetic susceptibility through white blood cells (lymphocytes) targeting autoantigens (key proteins in the body) on various tissues and organs. Extensive studies by ourselves, and others, have identified critical autoantigens which predict T1D. Indeed, abnormal responses to these autoantigens have been described, which result in destruction of autoantigen-expressing cells (e.g. insulin-secreting cells in the pancreas in T1D); an attack on tissues that probably results from a breakdown of immunological tolerance.
The thymus processes a type of white blood cell known as a T lymphocyte. These T lymphocytes govern cellular immunity which means they help cells recognise and destroy invading pathogens (e.g. bacteria and viruses), abnormal cells such as cancer, and foreign tissue. Immune tolerance to self-antigens is largely established centrally in the thymus, and peripherally by regulatory T lymphocytic cells.
At least one T1D-associated autoantigen, insulin, is associated with altered expression levels in the thymus of T1D patients. However, it remains unclear whether the same is true for other T1D-associated autoantigens. Interestingly, identical twins are often discordant for diabetes and autoimmune changes including autoantibodies to autoantigens. Thus, immune tolerance is likely also, in part, determined by non-genetically determined events. The aim of this work is to collect fresh thymus tissues discarded during routine cardiac surgery, extract selected cells and analyse the DNA profiles. These DNA profiles will be compared with DNA extracted from the spleen and pancreatic lymph nodes from controls and T1D patients (provided by nPOD). All samples will be compared to genes implicated in disease-associated immune dysfunction and control tissue to validate existing data from peripheral blood.REC name
London - Queen Square Research Ethics Committee
REC reference
14/LO/2132
Date of REC Opinion
27 Nov 2014
REC opinion
Favourable Opinion