How early does MS begin? #MSBlog #MSResearch
"This article of for the immunology geeks out there. What it shows that in children with MS there are changes in the immune system that mirror what is seen in adults. In other words the immune system of children with MS have already aged; this is called premature immunosenescence This study further implicates the immune system in the pathogenesis of MS and suggests that it has been overactive for sometime before the diagnosis is made. What are the implications of this study? It supports MS having a long presymptomatic phase; however, already know this from migration, twin and CIS studies."
"If you migrate from a high MS risk area to a low MS risk area as an adolescent or young adult you take your risk with you. In other words MS has already been triggered in the high-risk area. You can't undo our exposure. This has implications for MS prevention trials."
"When you do MRIs on identical twins of MSers you find that a lot of them have lesions typical of MS, but they have not yet developed symptoms of MS. These twins have what I call asymptomatic MS. The latter may be commoner than we think. A post-mortem study in Denmark suggests as many as 25% of people who have evidence of MS at death never get diagnosed in life. At the moment we call asymptomatic MS detected using RIS (radiologically isolated syndrome)."
"Finally, the majority of CISers when they present with MS have other lesions on their MRI that can't account for their symptoms. These other lesions are usually old, in other words they don't enhance with gadolinium. These older lesions tell us that MS started months or even years earlier. What determines if a lesion will causes symptoms, or not, is its size and location. It has to be placed in a clinically eloquent area. Does this mean the lesions in areas that are not eloquent are benign and irrelevant? Not at all. The only reason that these ineloquent lesions don't show up is because we don't do tests to detect them. Most of these so called quite lesions are in areas that may, or may not, cause cognitive problems. In addition, the brain is able to compensate for damage by using other areas of the brain or pathways. The process by which the brain compensates for damage is complex, but we do know that it requires increased energy expenditure, which in itself has been linked to MS-related cognitive fatigue. We also know from pathological studies that these so called silent lesions are also associated with damage; demyelination, axonal transections and gliosis (scarring of the brain). So silent lesions are not good for you, which is why we take them seriously and include them in our monitoring process."
OBJECTIVE: To assess pediatric MSers for early signs of homeostatic and functional abnormalities in conventional (Tcon) and regulatory T cells (Treg).
METHODS: They studied the composition of the peripheral T-cell compartment and Treg function in a cross-sectional study with 30 pediatric MSers by multicolor flow cytometry and proliferation assays. Data were compared to those obtained from adult MSers (n = 26) and age-matched control donors (n = 67).
RESULTS: Proportions of naive T cells were 10%-20% higher in children than in adults, reflecting the age-related decline. Pediatric MSers, however, had clearly lower numbers of naive T cells, among them recent thymic emigrants (RTE), whereas percentages of memory T cells were increased. In the Treg compartment, reduced RTE numbers coincided with markedly dampened suppressive capacities of total Treg. These homeostatic changes in circulating T cells precisely paralleled the pattern seen in adult MS. As in adults, treatment with immunomodulatory drugs attenuated these alterations.
CONCLUSION: The homeostatic changes detected in the T-cell compartment in pMS are similar to those in adult-onset disease. With ratios between naive and memory T-cell subsets matching those of 20- to 30-years-older controls, signs of early thymic involution are already found in pMS, suggesting that an intrinsic compromise in thymic-dependent T-cell neogenesis might contribute to MS pathogenesis.