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Published on: September 22, 2023
Monozygotic twins discordant for intermittent allergic rhinitis differ in mRNA and protein levels
A-K M Sjogren1, F Barrenas, A Muraro
1The Unit for Clinical Systems Biology, Queen Silvia Children's Hospital, University of Gothenburg, Sweden.
Abstract:
Monozygotic (MZ) twins discordant for complex diseases may help to find disease mechanisms that are not due to genetic variants. Intermittent allergic rhinitis (IAR) is an optimal disease model because it occurs at defined time points each year, owing to known external antigens. We hypothesized that MZ twins discordant for IAR could help to find gene expression differences that are not dependent on genetic variants. We collected blood outside of the season from MZ twins discordant for IAR, challenged their peripheral blood mononuclear cells (PBMC) with pollen allergen in vitro, collected supernatants and isolated CD4+ T cells. We identified disease-relevant mRNAs and proteins that differed between the discordant MZ twins. By contrast, no differences in microRNA expression were found. Our results indicate that MZ twins discordant for IAR is an optimal model to identify disease mechanisms that are not due to genetic variants.
Insights
Monozygotic (MZ) twins discordant for intermittent allergic rhinitis (IAR) reveal gene expression differences not linked to genetics. This study highlights discordant MZ twins as a valuable model for uncovering non-genetic disease mechanisms in complex conditions.
Area of Science:
- Immunology
- Genetics
- Allergy Research
Background:
- Complex diseases often have multifactorial causes, involving both genetic and environmental factors.
- Monozygotic (MZ) twins, who share identical DNA, are valuable for dissecting genetic versus non-genetic contributions to disease.
- Intermittent allergic rhinitis (IAR) presents a unique model due to its seasonal nature and identifiable external triggers.
Purpose of the Study:
- To investigate gene expression differences in MZ twins discordant for IAR, aiming to identify disease mechanisms independent of genetic variations.
- To establish discordant MZ twins as a model for studying non-genetic disease mechanisms.
Main Methods:
- Blood samples were collected from MZ twins discordant for IAR during their non-allergic season.
- Peripheral blood mononuclear cells (PBMCs) were challenged in vitro with pollen allergen.
- mRNA and protein expression levels were analyzed in isolated CD4+ T cells and cell supernatants.
Main Results:
- Significant differences in disease-relevant mRNA and protein expression were identified between discordant MZ twins.
- No significant differences in microRNA expression were observed between the discordant twins.
- These findings suggest non-genetic factors influence gene expression in IAR.
Conclusions:
- MZ twins discordant for IAR serve as an effective model for identifying disease mechanisms not attributable to genetic variants.
- The study successfully pinpointed specific mRNA and protein differences related to IAR in a genetically identical discordant twin pair.
- This approach offers a novel pathway to understand the environmental and epigenetic factors driving complex diseases.
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