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Published on: November 23, 2013
Aberrant lncRNA and mRNA expression in patients with anti-N-methyl-d-aspartate receptor encephalitis
Xiaoyu Ma1, Wenbo Guo1, Zixuan Teng2
1Department of Neurology, The Second Qilu Hospital of Shandong University, Jinan, China.
Background:
Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a nervous autoimmune disorder discovered in the recent more than 15 years. To understand potential involvement of epigenetic mechanisms in pathogenesis of anti-NMDAR encephalitis, we initiated a study to compare the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNA (mRNAs) in patients of anti-NMDAR encephalitis and healthy controls.
Methods:
Eleven patients who were diagnosed with anti-NMDAR encephalitis were enrolled in our observational studies. Total RNA was extracted from patients' plasma and the expression levels of lncRNAs and mRNAs were determined. Differential expression analysis via RNA sequencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as a co-expression network of lncRNA-mRNA were performed in 5 patients and 5 healthy controls to evaluate potential the changes in expression patterns. The expression levels of certain lncRNAs and mRNAs were further validated in 11patients and 11 healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR).
Results:
It was found that a total of 83 lncRNAs and 2,345 mRNAs were differentially expressed in five patients with anti-NMDAR encephalitis compared with five healthy controls. Of those lncRNAs, 63 were upregulated and 20 downregulated, while 1,509 mRNAs were upregulated and 836 downregulated. GO and KEGG pathway analyses showed that a wide range of biological functions were perturbed during acute anti-NMDAR encephalitis. Differentially expressed genes were found to be involved in autoimmune, B cell signaling, neuroinflammation, or synaptic plasticity. qRT-PCR was conducted in 11 patients and 11healthy controls to further confirm the levels of six lncRNAs and four mRNAs, and the results were found to be consistent with those by RNA sequencing. The co-expression networks of lncRNA-mRNA were performed in some meaningful KEGG analyses, including chemokine signaling pathway, Long-term potentiation, B cell receptor signaling pathway and MAPK signaling pathway.
Conclusion:
Taken together, these findings suggest the involvement of a number of molecular pathways in anti-NMDAR encephalitis, some of which could serve as potential biomarkers to assist in diagnosis, treatment and prognosis.
Insights
This study investigated long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Findings reveal altered lncRNA and mRNA expression, suggesting potential biomarkers for this autoimmune neurological disorder.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently identified autoimmune neurological disorder.
- Epigenetic mechanisms, including long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression, may play a role in its pathogenesis.
Purpose of the Study:
- To compare lncRNA and mRNA expression profiles in patients with anti-NMDAR encephalitis and healthy controls.
- To identify potential epigenetic alterations contributing to anti-NMDAR encephalitis.
Main Methods:
- RNA sequencing was performed on plasma samples from anti-NMDAR encephalitis patients and healthy controls.
- Differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and lncRNA-mRNA co-expression networks were utilized.
- Quantitative real-time polymerase chain reaction (qRT-PCR) validated expression levels of selected lncRNAs and mRNAs.
Main Results:
- A significant number of lncRNAs (83) and mRNAs (2,345) were differentially expressed between patients and controls.
- Affected biological pathways included autoimmune responses, B cell signaling, neuroinflammation, and synaptic plasticity.
- Co-expression network analysis highlighted pathways such as chemokine signaling and B cell receptor signaling.
Conclusions:
- Altered lncRNA and mRNA expression patterns are associated with anti-NMDAR encephalitis.
- These molecular pathways and differentially expressed genes may serve as potential biomarkers for diagnosis, treatment, and prognosis.
