Identification of key genes as potential diagnostic and therapeutic targets for comorbidity of myasthenia gravis and COVID-19, 2024, Liyan Huang et al

Introduction: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Coronavirus disease 2019 (COVID-19) has a significant impact on the health and quality of life of MG patients and may even trigger the onset of MG in some cases. With the worldwide development of the COVID-19 vaccination, several new-onset MG cases and exacerbations following the COVID-19 vaccines have been acknowledged. The potential link between myasthenia gravis (MG) and COVID-19 has prompted the need for further investigation into the underlying molecular mechanism.

Methods and results: The differential expression analysis identified six differentially expressed genes (DEGs) shared by myasthenia gravis (MG) and COVID-19, namely SAMD9, PLEK, GZMB, JUNB, NR4A1, and NR1D1. The relationship between the six common genes and immune cells was investigated in the COVID-19 dataset. The predictive value of the shared genes was assessed and a nomogram was constructed using machine learning algorithms. The regulatory miRNAs, transcription factors and small molecular drugs were predicted, and the molecular docking was carried out by AutoDock.

Discussion: We have identified six common DEGs of MG and COVID-19 and explored their immunological effects and regulatory mechanisms. The result may provide new insights for further mechanism research.

https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1334131/full

 

The relevant autoimmune disorders
The diseases associated with the shared genes of MG and COVID-19 were retrieved from the DisGeNET network10 and checked manually (Table 2). All six genes were related to autoimmune diseases, and some were involved in influenza or virus diseases such as GZMB, JUNB, and NR4A1. Of note, GZMB was directly associated with MG. The result suggested an important role for these genes in autoimmune disorders and virus-related diseases.

Drugs prediction
Small molecular drugs regulating the shared six genes were retrieved from the DsigDB database and ordered by p-value. Ouabain, felodipine, pimozide, luteolin, and emetine were selected from the top 10 drugs through evidence assessment on PubMed (Table 3). AutoDock software was used to forecast the free energy of binding as well as binding modes. The binding energy matrix of the genes and drugs is displayed in Figure 8C. Negative binding energy is indicative of a spontaneous chemical reaction, with the magnitude of the value reflecting the strength of the interaction between the drug and the protein. The binding modes of luteolin and ouabain to the proteins expressed by common genes are depicted in Figure 9.

Conclusion
In the present study, we identified six shared genes (SAMD9, PLEK, GZMB, JUNB, NR4A1, and NR1D1) of MG and COVID-19 patients through bioinformatic analysis. This study may offer innovative perspectives on the pathogenesis and theoretical foundation for the targeted therapy of the two related diseases.