F.27. Meta-analysis of Genome Scans and Replication Identify CD6, ICSBP1, and TNFRSF1A as Novel Multiple Sclerosis Susceptibility Loci

Three Decades of Interferon-β in Multiple Sclerosis: Can We Repurpose This Information for the Management of SARS-CoV2 Infection?

“…Additionally, in MS, evidence on low serum levels of IFN in most patients (9) poses the basis for IFN use in MS treatment and paves the way for the investigation of endogenous defect of IFN signaling in MS. In line with this observation, the presence of SNPs and rare variants in genes involved in type I IFN signaling and antiviral pathways, namely IRF-8, STAT3, SOCS1, TYK2, ZC3HAV1, and OAS1, which may display transcriptional dysregulation in blood cells at distinct MS stages (10), were found to be altered by several published GWA studies in MS, confirming the hypothesis that an alteration of IFN-regulated antiviral responses could be linked to MS pathogenesis (11)(12)(13).…”

Nuclear Factor κB (NF-κB)–Mediated Inflammation in Multiple Sclerosis

“…With the advent of genome-wide association studies and other genetic technologies, a large set of MS susceptibility variants has recently been reported, some of which fall in or near genes that regulate the NF-κB pathway, such as NFKBIZ and RELA (25)(26)(27)(28)(29)(30)(31). Subsequent studies have noted increased levels of NF-κB in total peripheral blood mononuclear cells (PBMCs), CD3 + /CD4 + T cells, and monocytes from patients with MS (32,33).…”

Review: Identifying patient subtypes in multiple sclerosis and tailoring immunotherapy: challenges for the future

“…For most MS patients, therefore, the warfarin example illustrates the way forward: it is by combining different pieces of information together and collapsing them into a single estimate of risk or outcome that we can have an impact on diagnosis and management in the near term. We are most advanced in our understanding of MS susceptibility for which genetic markers are now being discovered at a rapid pace [De Jager, 2009;Aulchenko et al 2008;Comabella et al 2008;Hafler et al 2008Hafler et al , 2007. Today, up to 16 risk alleles have been discovered, and, outside of the major histocompatability complex, each has only a modest effect on disease risk, with odds ratios estimated to be between 1.15 and 1.25 [De Jager, 2009;De Jager et al 2008] We further estimate that 50100 such risk alleles may exist and that an ongoing, large collaborative experiment involving the International MS Genetics Consortium and the Wellcome Trust will identify most of these risk alleles as it explores the genetic architecture of over 11 000 subjects with MS in 2009.…”