Multiple sclerosis (MS) can cause a huge range of symptoms in different patients, and the severity can vary dramatically. It is an inflammatory condition in which the body attacks myelin sheaths, a protective insulation surrounding nerve cells. This can cause fatigue, pain, paralysis, and symptoms that gradually get worse. MS can be very difficult to diagnose because the symptoms can be so different in different patients, and the presence of brain lesions is the clearest indication of the disease. MRIs that can reveal those brain lesions are only useful once the disease have progressed to the point of brain damage, however.
The innate immune system presents a potential option for monitoring the progression of MS. The disease causes inflammation, so researchers tracked immune cells in the brain called macrophages, and assessed brain inflammation in a mouse model of MS. The findings have been reported in Science Translational Medicine.
The investigators found a protein in the brains of the mice that allowed them to distinguish between normal and harmful inflammation. TREM1 is an innate immune cell receptor, and by using positron emission topography (PET) imaging on the TREM1 receptor, the researchers were able to reveal bad neuroinflammation with fourteen to seventeen times more sensitivity than current methods. When 178 different mice were given PET scans, the scientists found that TREM1 was only illuminated in mice with MS, and both before and after other symptoms arose.
"The mice looked completely normal, but we saw this blazing signal where cellular events were already occurring, creating damage," said senior study author Michelle James, PhD. "With this new non-invasive imaging approach, we can detect toxic inflammation that could help us better understand and treat diseases."
When the location of TREM1 was monitored, the researchers determined that immune cells had invaded the brain and spinal cord from outside the central nervous system. These abnormally localized cells led to serious damage. In mice in which the TREM1 gene was inactivated, inflammation was ablated.
A study of human samples confirmed that TREM1 was activated in MS patients. The study authors suggested that not only can TREM1 be used to diagnose MS, it could open up treatment options.
Not all disorders involving the destruction of the myelin sheath are necessarily MS, however. In a new study reported in JAMA Neurology, scientists have used patient samples to reveal a biomarker that can identify patients who have a subtype of an MS-like illness called central nervous system demyelination. This biomarker is a type of antibody that appears to attack a portion of the myelin sheath called myelin oligodendrocyte glycoprotein (MOG).
"There's a huge amount of diversity in how inflammatory autoimmune diseases of the central nervous system like multiple sclerosis present," noted Professor Anne-Katrin Pröbstel of the University of Basel and University Hospital Basel.
Central nervous system (CNS) demyelination diseases include neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody–associated disease.
Sources: Stanford University, University of Basel, JAMA Neurology, Science Translational Medicine
