Multiple Sclerosis: Shall We Target CD33?

Abstract

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.

Impact of Body Mass Index on the Age of Relapsing-Remitting Multiple Sclerosis Onset: A Retrospective Study

“…Its genetic background is known to be strong, with numerous susceptibility foci having been identified [11], and more than 110 genetic risk factors of MS have been pinpointed [12,13], though the genetic components alone do not suffice to explain its occurrence, as shown by the fact that homozygotic twins do not present the exact same rates of MS [14]. In fact, the genetic risk loci, alongside major risk HLA variants, can only explain approximately 30% of MS heritability, revealing the strong contribution of environmental factors to MS pathophysiology [15][16][17][18]. In this regard, various environmental factors have been pinpointed as risk factors for MS, such as viral infections [19], and interactions between specific polymorphisms and environmental risk factors have also been documented [20,21].…”

Thinking Outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke

“…Moving on, MS and IS share several other common elements besides neuroinflammation. Firstly, the genetic background of MS is indisputable [10,84,85]. Recent reports have claimed that MS and IS are also genetically linked [86], with numerous shared genes and similar gene expression levels [87].…”

CD33 mRNA Has Elevated Expression Levels in the Leukocytes of Peripheral Blood in Patients with Late-Onset Alzheimer’s Disease

“…Thus, with the loss of CD33 inhibitory activity, CD33 gene could have a role in NMOSD pathogenesis through the regulation of the immune system. In a recent study, Siokas et al [36] have reported that CD33 rs3865444 polymorphism is associated with multiple sclerosis that shares some similarities with NMOSD, and like NMOSD, is an inflammatory disease. The results indicated that CD33 rs3865444 polymorphism could be associated with the risk of multiple sclerosis in the dominant (OR [95% CI] = 0.79 [0.63-0.99], p = 0.041) and overdominant (OR [95% CI] = 0.77 [0.61-0.97], p = 0.03) genetic models.…”