Analyzing Certain Immune Cells in Thymomas May Help to Predict MG
Determining whether two types of immune cells — T follicular helper cells and activated dendritic cells — are present or lacking in a thymoma, in addition to the levels of specific genes, may help to predict the risk of myasthenia gravis (MG) among people with these tumors, a small study suggests.
The study, “Two types of immune infiltrating cells and six hub genes can predict the occurrence of myasthenia gravis in patients with thymoma,” was published in the journal Bioengineered.
Rare tumors in the thymus gland, commonly known as thymomas, are found in up to 15% of MG patients. These people often have a poorer prognosis, which supports the need to further understand which immune cells may infiltrate and associate with such tumors.
To help in this, a team of researchers at Tianjin Medical University General Hospital, in China, analyzed RNA sequencing data from 78 thymoma tissues (53 without and 25 with MG) obtained from The Cancer Genome Atlas database.
An additional set of 40 tissue samples (34 thymomas and six normal tissues) from the Gene Expression Omnibus database were also analyzed.
RNA sequencing allows the analysis of the transcriptome — the entire set of messenger RNA molecules constituting copies of the DNA sequence used to build proteins.
The analysis revealed an enrichment of two types of immune cells — called T follicular helper cells (Tfh) and CD8-T cells — in thymomas associated with MG relative to thymomas without it. CD8-T cells have an important role in fighting infections, and Tfh cells play a key role in the production of antibodies against pathogens.
In contrast, significantly lower levels of three subtypes of macrophages —M0, M1 and M2 — and of regulatory T-cells (Tregs), a specialized T-cell subpopulation that acts to suppress the immune response, were found in thymomas associated with MG.
Two other types of immune cells — called eosinophils and activated dendritic cells (DCs) — were present in certain thymoma samples, but not in those associated with MG.
Analysis of the Gene Expression Omnibus data confirmed the results seen in the Genome Atlas sample group. The combination of these data suggests that “Tfh cells and activated DC were involved in thymoma induced MG,” the researchers wrote.
To confirm the immune status of thymomas, the team further analyzed individual genes and found that 27 had significantly changed levels between thymomas with and without MG.
From these, only six genes — HMGA1, MTA1, EZH2, FOS, TP53, and TFAP2A — showed statistically significant differences.
Further analysis and prediction models suggested that the levels of Tfh cells and these genes — namely HMGA1, TP53, and TFAP2A — were good predictors of MG in thymoma patients.
“The results showed that Tfh cells and genes such as HMGA1, TP53 and TFAP2A could effectively predict MG occurrence in thymoma patients,” the researchers wrote. “These genes affect the expression [the levels] and function of immune cells, thus predicting the occurrence of MG in patients with thymoma.
“We hope these results can provide novel point in the causes of MG, thus helping clinicians in evaluating the diagnosis, treatment, and then improving the prognosis of thymoma with MG,” they concluded.