Search of prognostic biomarkers in patients with multiple sclerosis
Year: 2014
Type: dissertation
Study design: Observational Study
Abstract: The aim of the thesis was to identify biomarkers for multiple sclerosis (MS) prognosis, in particular disease activity biomarkers and interferon-β (IFNβ) treatment response biomarkers. The results presented in this thesis show an increase in the expression of sialic acid binding Ig-like lectins 1 (SIGLEC1) in progressive phases of MS (particularly during primary progressive MS - PPMS). Detailed analysis has demonstrated that both inflammatory and resident monocytes contributed to increased SIGLEC1 expression in PPMS. We also reported that SIGLEC7 expression was elevated in relapsing-remitting MS (RRMS) patients during relapses. Our results also indicate deficient expression of ubiquitin specific peptidase 18 (USP18) in RRMS patients as compared to controls. Further investigation revealed that haplotype CG carriers showed lower USP18 gene expression levels and higher clinical disease activity compared to CG non-carriers. Moreover, AA homozygosis for an intronic polymorphism of USP18 was associated with the responder phenotype. In conclusion, our results suggest the implication of SIGLEC1 in chronic progressive phases of MS and of SIGLEC7 in acute disease activity. We also demonstrated the implication of USP18 in MS pathogenesis and the therapeutic response to IFNβ. Based on these results, we propose SIGLEC1, SIGLEC7 and USP18 as potential disease activity biomarkers of MS, and USP18 as response biomarker to IFNβ.
Author: Sunny Malhotra
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2509248415