Unveiling Immune Dysregulation: Insights into FOXP3 Expression and Ancestry Associations in Neuromyelitis Optica Spectrum Disorder in Patients from Bogotá, Colombia.
Luis Ibarra1, Juliana Lago2, Jairo Gaitan Alfonso1, Daniela Rodriguez1, Juan Rodriguez noriega1, Saul Reyes1, Diana Narvaez2, Jaime Toro3, Helena Groot2
1Fundación Santa Fe de Bogotá University Hospital, 2Human Genetics Laboratory, Universidad de los Andes, 3Universidad El Bosque
Objective:
To compare FOXP3 expression between NMOSD patients and controls and evaluate its relationship with genetic ancestry in a Bogotá-based cohort.
Background:
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system characterized by relapses involving the optic nerve and spinal cord, with epidemiologic variation across regions and ethnic groups. FOXP3, a transcription factor in CD4⁺ regulatory T cells (Treg), is essential for immune tolerance. In this cohort, we quantified FOXP3 expression in NMOSD versus controls and assessed its relationship with genetic ancestry.
Design/Methods:
In this cross-sectional exploratory study, peripheral blood mononuclear cells (PBMCs) were isolated, RNA was extracted, reverse-transcribed into cDNA, and FOXP3 expression was measured by qPCR, normalized to β-actin. Relative quantification used the 2−ΔCt method. Genetic ancestry proportions were estimated through Ancestry Informative Markers (AIMs). Stratified regression analyses tested associations between FOXP3 expression and ancestry, adjusting for disease status.
Results:
Twenty-six NMOSD patients and fifteen controls were analyzed. FOXP3 expression was reduced in NMOSD compared with controls (p=0.027). Patients with atypical optic neuritis had lower FOXP3 than those without this presentation (p=0.0059). After adjusting for disease status, FOXP3 expression showed significant associations with African (p=0.035) and Native/Indigenous American ancestry (p=0.012).
Conclusions:
FOXP3, the hallmark transcription factor of Tregs, is essential for maintaining immune tolerance. In our cohort, FOXP3 expression was decreased in NMOSD compared with controls. Among NMOSD patients, African and Indigenous American ancestry correlated with FOXP3 levels. These findings provide insight into immune mechanisms and biological heterogeneity across populations and warrant further studies to clarify the role and importance of FOXP3 in NMOSD.
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