Multiple Sclerosis (MS) is the most common chronic neurological disease of young adults in Australia, yet cause is unknown and there is no cure. MS is an autoimmune disease, in which the immune system inappropriately targets the myelin coating of nerves in the brain and spinal cord. This results in impaired nerve conduction and a myriad of neurological symptoms, ranging from fatigue to paralysis and severe disability. MS begins in most people with neurological attacks interspersed with periods of remission, or “relapsing-remitting” MS. With repeated attacks over time, damage to the brain and spinal cord cannot be repaired, and a “secondary progressive” course with cumulative and permanent disability ensues.
MS is thought to be triggered by environmental factors such as infection with Epstein Barr virus (EBV; the virus that causes glandular fever) in people who are genetically susceptible. In earlier studies, Dr McKay showed that two genes involved in increased risk of MS were found at lower levels in a specific type of immune cell called natural killer cells in people with MS. Intriguingly, natural killer cells are important in the body’s first line of defence against EBV infection. They are also able to kill other immune cells in the body that drive the autoimmune process, called T cells, thus are implicated in control of autoimmune disease. Harnessing natural killer cells for improved killing of EBV and autoimmune T cells is a potentially powerful therapeutic option for MS, but greater understanding of natural killer cells in MS is required.
There are many types of natural killer cells with varied functions. The primary aim of this project was to deeply characterise the types of natural killer cells in MS. This involved working very closely with industry, and the Flow Cytometry unit and bioinformaticians at the Westmead Hub to develop a panel of fluorescent markers and data analysis pipeline to measure 23 functional immune molecules on natural killer cells in MS. The analysis method was presented at NK 2019, Luxembourg, and Progress in MS Research, Melbourne, 2019 and has fostered multiple collaborations described below. Using the analysis methods developed, Dr McKay characterised 20 natural killer typesin the blood of 73 people with MS compared to people without MS. Several important types of natural killer cells were found at lower numbers in the blood of people with secondary progressive MS. This is intriguing given recent literature suggesting that EBV infection is prominent in the brain in this stage of MS. Ongoing work is addressing the capacity of various types of natural killer cells to kill cells infected with EBV, and whether this killing can be enhanced by repurposed therapies used to stimulate natural killer cells in other diseases such as cancer.