Multiple sclerosis and neuromyelitis optica spectrum disorders: some similarities in two distinct diseases

Yokote, Hiroaki; Mizusawa, Hidehiro

doi:10.4103/1673-5374.179048

Cited by 15 publications

(3 citation statements)

References 12 publications

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“…More precisely, this 19-base pair deletion variant (chr19:51729579e51729597delCCAACAACTGGTATCTTTC), located exon 4 of the CD33 gene, results in a frameshift mutation with premature truncation (c.712-730delCCAACAACTGGTATCTTTC, p.Pro238Glnfs*38), leading to nonsense-mediated decay or to a shorter protein lacking 30 C-terminal amino acids [ 18 ]. This is intriguing, given that NMOSD and MS share some similarities despite the fact that they are two distinct diseases [ 19 ]. More precisely, microglial infiltration and lipid-laden macrophages, despite not being a landmark of the disease, have been reported in NMOSD [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…More precisely, microglial infiltration and lipid-laden macrophages, despite not being a landmark of the disease, have been reported in NMOSD [ 45 ]. Another similarity between NMOSD and MS is the cytokine profile, as recent studies suggest that the pathophysiology of both diseases includes Th17-mediated pathways, mainly responsible for demyelination [ 19 , 46 ]. However, how and to what extent CD33 affects the immune system and possibly contributes to these diseases can only be speculated at the moment.…”

Section: Discussionmentioning

confidence: 99%

“…A frameshift variant in the CD33 gene has emerged as a potential risk locus for neuromyelitis optica spectrum disorder (NMOSD) [ 18 ], a disease that shares some similarities with MS [ 19 ]. Moreover, from a genetic point of view, CD33 rs3865444 is a common promoter variant, which appears to modify CD33 function and has also been previously associated with the commonest neurodegenerative disease, i.e., Alzheimer’s disease (AD) [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Multiple Sclerosis: Shall We Target CD33?

Siokas

Tsouris

Aloizou

et al. 2020

Genes

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Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Myeloid lineage cells (microglia and macrophages) may participate in the pathogenic mechanisms leading to MS. CD33 is a transmembrane receptor, mainly expressed by myeloid lineage cells. CD33 rs3865444 is a promoter variant previously associated with Alzheimer’s disease, whose role in MS remains obscure. Objective: To assess the role of CD33 rs3865444 in MS risk. Methods: We genotyped 1396 patients with MS and 400 healthy controls for the presence of the CD33 rs3865444 variant. Odds ratios (ORs) with the respective 95% confidence intervals (CIs), were calculated with the SNPStats software, assuming five genetic models (co-dominant, dominant, recessive, over-dominant, and log-additive), with the G allele as the reference allele. The value of 0.05 was set as the threshold for statistical significance. Results: CD33 rs3865444 was associated with MS risk in the dominant (GG vs. GT + TT; OR (95% C.I.) = 0.79 (0.63–0.99), p = 0.041) and the over-dominant (GG + TT vs. GT; OR (95% C.I.) = 0.77 (0.61–0.97), p = 0.03) modes of inheritance. Given that the GG genotype was more frequent and the GT genotype was less frequent in MS patients compared to controls—while the observed frequency of the TT genotype did not differ between the two groups—the observed difference in MS risk may be stemming from either the GG (as a risk factor) or the GT (as a protective factor) genotype of CD33 rs3865444. Conclusions: Our preliminary results suggest a possible contribution of CD33 rs3865444 to MS. Therefore, larger multiethnic studies should be conducted, investigating the role of CD33 rs3865444 in MS.

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Section: Discussionmentioning

confidence: 99%