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New Study Suggests Immune Genes Help Determine Sites of MS Damage and Symptoms

May 29, 2008

New Study Suggests Immune Genes Help Determine Sites of MS Damage and Symptoms

Australian investigators funded by the National MS Society (USA) and MS Australia have published results suggesting that a person’s set of immune-related genes may help determine which parts of the brain and spinal cord are attacked by the immune system during the course of their MS, and may explain why individuals with MS experience tissue damage, and corresponding symptoms, differently. Judith M. Greer, PhD, and colleagues (University of Queensland, Australia) report their findings in the May 1 issue of

The Journal of Immunology

(2008,180:6402-6410).

Background: A complex issue in MS research is that the areas in the brain and spinal cord in which damage to nerve-insulating myelin occurs can vary dramatically from person to person. The sites targeted by the immune attack have a profound impact on the types of symptoms a person is likely to experience. In MS, immune cells called T cells appear to mistakenly react against a variety of myelin proteins. Previous studies have hinted that the particular myelin protein that triggers this immune response may be correlated with different locations of myelin damage. Dr. Greer’s team has been examining a possible link between a genetically determined molecular “ID tag” – called the human leukocyte antigen (HLA) – carried on a person’s cells, and the location of MS lesions.

This Study: The group tested T cell and immune antibody reactivity in blood samples from 100 people with MS, 70 people without MS, and 48 people with other neurological disorders. Forty of the people with MS showed increased reactivity to one or more myelin proteins, compared to those without MS. Of those, the team found a highly significant correlation between reactivity to specific portions of a major myelin protein called proteolipid protein (PLP) and development of lesions in the brainstem (the lowest part of the brain) and cerebellum (the back of the brain). Clinical symptoms associated with these types of lesions include abnormalities of eye movement or weakness, difficulty with speech and swallowing, loss of sensation in the face, facial pain called trigeminal neuralgia, and others. Lesions in the brainstem and cerebellum also significantly correlated with those carrying specific HLA genes – HLA-DR4, HLA-DR7, or HLA-DR13.

"This study provides us with a new clue as to why people with MS have such different experiences,” says John R. Richert, MD, Executive Vice President of Research & Clinical Programs for the National MS Society. “It will be important to expand and build on these results. Explaining the biologic basis for differences in MS-related damage may lead to more targeted treatment strategies and better ways of predicting the course of MS.”