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Published on: October 28, 2020
IL28B, IL29 and micro-RNA 548 in subacute sclerosing panencephalitis as a rare disease
Gunes Cakmak Genc1, Ahmet Dursun1, Sevim Karakas Celik2
1Faculty of Medicine, Department of Medical Genetics, Bulent Ecevit University, Zonguldak, Turkey.
Abstract:
Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease which affects children and young adults, caused by a persistent infection of defective measles virus. IFN-λs (IL-28A, IL-28B and IL-29) are a group of cytokines mediating antiviral responses. It has been shown that IL-29 levels are significantly higher in infected cells with defective measles virus. IL-29 expression is thought to be regulated at post-transcriptional level and miRNA-548 family targets the 3'UTR of the IFNL1 gene. Impaired immune system has an important role as well as viral factors in SSPE. The aim of our study investigates whether IL-28B, IL-29 levels and gene polymorphisms contribute to the damaged immune response leading to the development of SSPE. Also possible association of miR-548 family with IL-29 and SSPE is explored. Frequencies of rs12979860, rs8099917, rs30461, serum levels of IL-28B, IL-29 and expression levels of miR-548b, miR-548c, miR-548i are determined at 64 SSPE patients and 68 healthy controls. Serum IL-29 levels are statistically significant higher in SSPE patients. Allele frequencies of rs8099917 are statistically significant higher in SSPE patients and resulted G allele is found to increase 2.183-fold risk of SSPE. The expression levels of miR-548b-5p, miR-548c-5p and miR-548i are found to be statistically significant higher in SSPE patients. Dramatically increased level of IL-29 seen in patient group indicates that the elevated miR-548 expression is compensatory result of the over-activated immune system response. Further studies referred to IL28, IL29 and related miRNA's will be enlightened the pathogenesis of SSPE.
Insights
Subacute sclerosing panencephalitis (SSPE) involves higher levels of interleukin-29 (IL-29) and specific microRNAs (miRNAs) in patients, suggesting an overactive immune response. Gene variations like rs8099917 also increase SSPE risk.
Area of Science:
- Immunology
- Neuroscience
- Virology
Background:
- Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by persistent measles virus infection.
- Interferon-lambdas (IFN-λs), including IL-28B and IL-29, are crucial cytokines in antiviral responses.
- Elevated IL-29 levels and altered immune responses are implicated in SSPE pathogenesis.
Purpose of the Study:
- To investigate the contribution of IL-28B, IL-29 levels, and gene polymorphisms to immune dysfunction in SSPE.
- To explore the association between the miR-548 family, IL-29, and SSPE development.
- To identify potential biomarkers for SSPE risk and progression.
Main Methods:
- Genotyping for IL28B polymorphisms (rs12979860, rs8099917, rs30461) in 64 SSPE patients and 68 controls.
- Quantification of serum IL-28B and IL-29 levels.
- Measurement of miR-548b, miR-548c, and miR-548i expression levels in patients and controls.
Main Results:
- SSPE patients exhibited significantly higher serum IL-29 levels compared to healthy controls.
- The G allele of the rs8099917 polymorphism was significantly more frequent in SSPE patients, increasing SSPE risk 2.183-fold.
- Expression levels of miR-548b-5p, miR-548c-5p, and miR-548i were significantly elevated in SSPE patients.
Conclusions:
- Elevated IL-29 and miR-548 expression in SSPE patients may represent a compensatory immune response.
- Specific IL28B gene polymorphisms, particularly rs8099917, are associated with increased SSPE risk.
- These findings highlight the role of specific cytokines and miRNAs in SSPE pathogenesis and suggest potential therapeutic targets.
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