Immunoglobulin A Antibodies as Biomarker for Multiple Sclerosis Progression
Abstract
Our immune system protects us against pathogens like bacteria, viruses, and parasites. An important component of the immune system are antibodies. These are molecules that are present in large quantities in our body. They have two sides. One side can bind to pathogens, whereas the other side can bind to immune cells. In this way, antibodies bridge pathogens and immune cells, after which the immune cells can eliminate the pathogens. Unfortunately, sometimes the immune system goes awry, and starts producing antibodies against our own body, which enables immune cells to attack our own tissues. This is referred to as autoimmunity (auto = self), and the antibodies are now referred to as autoantibodies. Patients with multiple sclerosis (MS) also develop autoantibodies, which can be found in the nervous system. Two different types of autoantibodies, IgG and IgA, have been detected. Whereas most research focuses on the role of IgG in MS, we recently discovered that IgA, especially, is extremely potent in triggering immune cells. Hence, we hypothesize that the production of auto-IgA in MS patients causes excessive activation of immune cells, which leads to severe damage to the brain. As such, we predict that the presence of IgA in the spinal fluid represents a novel measurable indicator (a so-called biomarker) of disease activity and progression. In this project, we aim to determine whether levels of auto-IgA in spinal fluid from MS patients correlates with disease severity and progression. Secondly, we aim to correlate the presence of IgA-producing B cells with local tissue damage in post-mortem brain tissue of MS patients. Therefore, this project addresses the FY19 MSRP Focus Area "Correlates of Disease Activity and Progression in MS." Results from this project could benefit MS patients in several ways. First, there is an urgent need for a suitable biomarker for MS disease progression. If our experiments indeed indicate that IgA can be used as a biomarker, this will facilitate clinical trials aimed at treating progressive MS. Secondly, measuring IgA levels in both relapsing-remitting and progressive MS patients could help to decide which treatment options are most suitable for individual patients. And, lastly, if we successfully demonstrate the deleterious effect of IgA autoantibodies on tissue damage and subsequent progression of multiple sclerosis, we can develop new therapies to counteract this process. Hopefully, these therapeutics will prove to be very effective in ameliorating disease, also in progressive MS patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jun 29, 2021
- Source ID
- W81XWH2010835
Entities
People
- Marjolein Van Egmond
Organizations
- United States Army