2 genes controlling body’s biological clock are dysregulated in MG
Study findings may offer treatment strategies for future research
Two genes that help to control the human body’s biological clock are dysregulated in myasthenia gravis (MG) — a disease marked by symptoms that often grow worse throughout the day — according to the findings of a new study from China.
Study data indicated that dysregulation of these genes, called CIRBP and USP30, is associated with alterations in disease-driving immune cells in MG, though the scientists highlighted a need for further research to verify the findings.
Still, the team wrote that these results “suggest a potential circadian rhythm disorder in MG, which may offer novel biomarkers and therapeutic strategies for future research.”
The study, “Circadian rhythm genes and immune cell infiltration in myasthenia gravis: A comprehensive analysis,” was published in the journal PLOS One.
The circadian rhythm is the series of biological changes that happen within the body over the course of a day. These changes are crucial in regulating a series of bodily functions, including sleep patterns, appetite, and immune responses.
MG is an autoimmune disorder that causes muscle weakness. People with MG commonly report that disease symptoms are milder in the morning and then get more severe as the day goes on. The commonness of daily fluctuations in MG symptoms implies a potential relationship between MG and circadian rhythms, according to the scientists.
Researchers zero in on 2 genes regulating circadian rhythm
To explore this potential relationship, a research team from the Changchun University of Chinese Medicine conducted a detailed analysis using a dataset that included genetic and cellular data. That data came from 13 MG patients and 12 people without any known disease.
The researchers first looked for differences in the activity of more than 5,000 genes known to be associated with the body’s circadian rhythm. The team was able to identify more than 100 genes with significant differences in activity.
After further analysis, the scientists zeroed in on two circadian rhythm genes called CIRBP and USP30 as key markers of circadian rhythm problems in MG. Data indicated that the activity of both of these genes was significantly elevated in MG patients.
A separate analysis on blood samples from 20 MG patients and 20 healthy controls likewise showed that the levels of CIRBP and USP30 proteins, each encoded by their respective gene, were elevated in MG patients. Further statistical analyses indicated that elevated activity of the two genes showed “strong specificity, minimal false positives, and reliable accuracy in distinguishing MG patients from controls,” the researchers wrote.
[The findings suggest] that the disruption of immune cell balance … and abnormal expression of circadian rhythm genes are interrelated processes that collectively influence the [development] and progression of MG.
MG is driven by antibodies, which are proteins made by immune cells called B-cells. Analyses of the main dataset showed that the individuals with MG had alterations in B-cell counts. Specifically, the patients had higher levels of naive immature B-cells, but lower levels of mature, antibody-making B-cells, known as plasma cells.
The researchers noted that CIRBP and USP30 gene activity showed statistically significant correlations with B-cell counts, with higher gene activity being associated with having a higher proportion of naive B-cells and fewer plasma cells. Other correlations between the two key circadian genes and immune cell dysregulation also were noted.
According to the team, the associations between circadian genes and immune cells suggest “that the disruption of immune cell balance … and abnormal expression of circadian rhythm genes are interrelated processes that collectively influence the [development] and progression of MG.”
Altogether, these data support the idea that MG may be marked by disruptions in the body’s circadian rhythm, particularly with relation to the activity of the CIRBP and USP30 genes.
The researchers stressed, however, that these analyses were based on data from a small number of patients, and that additional work will be needed to verify the findings and further explore the role of these genes in MG.
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