THE MYSTERY OF THE MISSING ANTIBODIES

One of the perennial questions of MS research is, what is it that triggers the attack on the nervous system in the first place? We have plenty of information about some of the genetic and environmental factors that can increase a person’s risk of developing MS (see our recent article here). But exactly what the first biological trigger is that causes the immune system to attack the nervous system remains a mystery.

We know that the ongoing damage to the myelin sheath that protects nerve fibres is driven by autoimmune processes, where a person’s immune system turns on their own body. However, in the majority of autoimmune diseases, scientists have been able to identify antibodies in the bloodstream that are specific to that disease and inappropriately attack the tissues affected in those diseases. Antibodies are normally produced by the immune system to respond to invading micro-organisms, such as bacteria and viruses. In autoimmune diseases, antibodies are produced that mistakenly recognise a part of the human body instead.

Many studies seeking to identify the antibodies that might trigger MS, conducted over many years, have produced conflicting results. Some researchers have found antibodies that appear to specifically target the central nervous system, but others have been unable to confirm these findings.

Two Australian researchers who have been diligently pursuing this line of research are Dr John Parratt and Professor John Prineas of the Brain and Mind Centre at the University of Sydney. Dr Parratt was the recipient of the MS Research Australia Neil and Norma Hill Clinical Research Fellowship from 2010 to 2013.

Dr Parratt and Professor Prineas, have recently published their findings from this study in the Multiple Sclerosis Journal. In this study they conducted a detailed ‘survey’ of the antibodies present in the blood of people with MS.

They collected blood samples from 106 people with MS, 156 people with other neurological diseases and 70 people with no neurological disease. They then screened these samples for brain-specific antibodies, using a technique in which the samples are washed over slices of brain tissue. The tissue is then examined under the microscope to see if any antibodies have stuck to the brain cells.

The researchers found a whole range of antibodies in the samples that bound to the brain tissue. Some had never been detected before in other studies and appeared to very specifically ‘stick’ to certain types of brain cells. This is an exciting finding in itself, which the researchers attribute to the novel technique they used to process the brain tissue. They will be investigating these antibodies in more detail.

However, despite these antibodies being quite common in the blood of people with MS, disappointingly, none of the antibodies seemed to be unique to people with MS. They were also found in the healthy individuals and those with other neurological diseases, suggesting they may not be specifically causing MS.

The authors discuss a range of studies over the years that have examined brain tissue from people with MS for the presence of antibodies and immune cells in the earliest stages of MS lesions. Again the results have been conflicting and hotly debated. Several studies, including a pivotal study conducted by Professor Prineas and colleagues more than 10 years ago, suggested that the very earliest signs of myelin damage were not associated with immune cells or antibodies.

And so the results of Dr Parratt’s and Professor Prineas’ current study, and several of those that have preceded it beg the question: If it is not a myelin-specific antibody that triggers myelin damage in MS, then what is it?

Is it a problem in the myelin producing cells themselves that causes them to begin dying? This could then trigger the immune and support cells in the brain to respond to clean up the damage and that in turn triggers a bigger immune response. Or is it a flaw in the immune system (which some of the genetic studies suggest) that allows the immune cells to become ‘trigger happy’ and set off an inflammatory response in the brain with minimal or no provocation?

The mystery continues. But what is certain is that the work done by Dr Parratt and Professor Prineas helps us to rule out some possibilities and allows us to keep moving down other lines of investigation to bring us closer to solving the mystery.

Article courtesy of MS Research Australia www.msra.org.au