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Multiple Sclerosis: Shall We Target CD33?
Vasileios Siokas1, Zisis Tsouris1, Athina-Maria Aloizou1
1Laboratory of Neurogenetics, Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.
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.
Insights
The CD33 rs3865444 genetic variant shows a potential link to multiple sclerosis (MS) risk. Further multiethnic studies are needed to confirm its role in MS pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease.
- Myeloid cells like microglia and macrophages are implicated in MS pathogenesis.
- CD33 is a myeloid cell receptor, and the rs3865444 variant's role in MS is unknown.
Purpose of the Study:
- To investigate the association between the CD33 rs3865444 variant and the risk of developing MS.
Main Methods:
- Genotyping of 1396 MS patients and 400 controls for the CD33 rs3865444 variant.
- Statistical analysis using SNPStats software under five genetic models.
- Calculation of odds ratios (ORs) and 95% confidence intervals (CIs), with p<0.05 as significance threshold.
Main Results:
- The CD33 rs3865444 variant was significantly associated with MS risk under dominant and over-dominant inheritance models.
- The GG genotype was more frequent in MS patients, while the GT genotype was less frequent, suggesting a potential risk or protective role.
- The TT genotype frequency did not differ between MS patients and controls.
Conclusions:
- Preliminary findings suggest CD33 rs3865444 may contribute to MS risk.
- Larger, multiethnic studies are recommended to further elucidate the role of CD33 rs3865444 in MS.
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