Graduation Date

Spring 5-5-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Immunology, Pathology & Infectious Disease

First Advisor

Kaihong Su

Abstract

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with varying clinical presentation and severity in different ethnicities/races. Micro-RNAs (miRNAs) modulate the immune system, and there is a growing interest in their role in SLE pathogenesis and disease presentation. Studies on miRNAs expression in SLE have been done in Caucasians and Asians but no comprehensive profiling has been done in Hispanics. This cross-sectional study of a Hispanic cohort of SLE patients (n =185) and healthy controls (HC) (n =185) from the Dominican Republic determined the expression of 10 selected miRNAs and their correlation to inflammatory markers and auto-antibody production in SLE. The expression levels of miR-451a miR-16-5p, miR-126-5p, miR-146a-5p were significantly higher in SLE patients than in HC. miR-125a-3p and miR-155-5p were lower in SLE while miR-21-5p, miR-142-3p, miR-148a-3p, and miR-223-5p showed no difference between SLE and HC. MiR-16-5p correlated with anti-Sm and IFN-γ; miR-155-5p correlated with anti-SSA/Ro, IL-1β, and IL-12p70; and miR125a correlated with C4 and IL-1β. We also show that miR451a and miR125a affect activation of neutrophil-like NB4 cells, pointing to their potential role in neutrophil-mediated inflammation in SLE. This novel study in a Hispanic cohort shows differential expression of miRNAs in SLE and significant correlation with markers of inflammation, setting an important premise for further study on their mechanism of action.

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