New genetic markers may make prognosis clearer
https://www.ms-uk.org/new-genetic-marke ... is-clearer
The original paper:
Early complement genes are associated with visual system degeneration in multiple sclerosis
https://academic.oup.com/brain/article- ... m=fulltext
"In conclusion, early complement pathway gene variants were consistently associated with structural and functional measures of multiple sclerosis severity. These results from unbiased analyses are strongly supported by several prior reports that mechanistically implicated early complement factors in neurodegeneration."
https://onlinelibrary.wiley.com/doi/ful ... 03.02238.x
Glatiramer acetate (GA) is effective in the treatment of Multiple Sclerosis (MS) presumably by the induction of an immunoregulatory T‐cell response.
We have previously shown that GA directly induces the Th2 cytokines IL‐13 and IL‐5 in T‐cells in vitro. In the present study we compared the in vitro response to GA in healthy controls, untreated and GA‐treated MS patients and tested whether the induction of IL‐13 and IL‐5 secretion is also detectable in the serum of 25 MS patients treated with GA. Patients were grouped into clinical responders and nonresponders in order to determine a possible correlation with the immunological response. As a result we found a significant increase of IL‐13 in the serum of clinical GA‐responders whereas IL‐13 was not detectable in controls, untreated MS (P < 0·001) and nonresponders (P = 0·015). Similarly, GA‐treatment increased serum levels of IL‐5 (P = 0·001). The correlation of serum IL‐5 and clinical response was also significant (P = 0·039), however, there was an overlap between the different groups.
The selective induction of IL‐13 and IL‐5 but not IL‐4 by GA treatment suggests that the specific biological functions of these cytokines might be important for the therapeutic mechanism of GA. Measurement of serum IL‐13 and IL‐5 levels is a simple and inexpensive tool for monitoring the response to GA in MS patients.
Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis
https://www.frontiersin.org/articles/10 ... 01008/full
Individual measures of CSF NFL and CHI3L1 are biomarkers of disease activity and progression, respectively. The pattern of combined measure discriminates MS phenotypes. It also predicts the subset of RRMS patients that will progress clinically allowing early intervention.
Biomarkers predicting fingolimod (FTY) treatment response in relapsing-remitting multiple sclerosis (RRMS) are lacking. Here, we performed extensive functional immunophenotyping using multiparametric flow cytometry to examine peripheral immune changes under FTY treatment and explore biomarkers of FTY treatment response. From among 135 RRMS patients who initiated FTY in a 2-year multicentre observational study, 36 were classified as ‘Active’ or ‘Stable’ based on clinical and/or radiological activity on-treatment. Flow cytometric analysis of immune cell subsets was performed on pre- and on-treatment peripheral blood mononuclear cells (PBMC) samples. Decreased absolute counts of B cells and most T-cell subsets were seen on-treatment. Senescent CD8 + T cells, CD56 + T cells, CD56dim natural killer cells, monocytes and dendritic cells were not reduced in number and hence relatively increased in frequency on-treatment. An unbiased multiparametric and traditional manual analysis of T-cell subsets suggested a higher pre-treatment frequency of CD4 + central memory T cells (TCM) in patients who were subsequently Active versus Stable on-treatment. Lower pre-treatment terminally differentiated effector memory (TEMRA) cell frequencies were also seen in the subsequently Active cohort. Together, our data highlight differential effects of FTY on peripheral immune cell subsets and suggest that pre-treatment T-cell subset frequencies may have value in predicting FTY treatment response.
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