Thyroid hormone FT4 may play role in development of MS
Elevated FT4 levels linked to increased MS risk in study
The thyroid hormone thyroxine, or FT4, may play an indirect role in the development of multiple sclerosis (MS), which seems to be mediated by certain immune cells, a study suggests.
“Future investigations should explore how these immune cells modulate MS onset and progression in the context of thyroid dysfunction, and how targeting these cells could lead to innovative MS interventions,” researchers wrote.
The study, “Thyroid function and multiple sclerosis: a two-sample mendelian randomization study and mediation analysis,” was published in Scientific Reports.
MS is caused by an inflammatory attack on the myelin sheath, a protective coating around nerve fibers that boosts the speed of nerve impulses. Damage to that sheath, as well as nerve cells themselves, gives rise to disease symptoms.
People with MS at higher risk of disorders affecting thyroid gland
Studies suggest people with MS are at a higher risk of disorders affecting the thyroid gland, such as Graves’ disease and Hashimoto’s disease. This butterfly-shaped gland is located at the base of the throat and produces hormones that control metabolism. It’s also been reported that thyroid hormones may play a role in myelin formation.
It remains unclear, however, whether there’s a causal relationship between MS and thyroid disorders. That is, does abnormal thyroid function cause MS, or conversely, does MS cause thyroid problems?
To address this, researchers in China conducted bidirectional Mendelian randomization, a statistical technique that uses genetic information to identify potential cause-and-effect relationships.
Genetic information came from genome-wide association studies (GWAS), which detect associations between genetic variants and a particular trait or disease. The team used GWAS data from large-scale studies on MS, thyroid function, and thyroid-stimulating hormone, or TSH, which triggers the release of other hormones from the thyroid, including FT4.
When researchers asked whether abnormal thyroid function causes MS, data showed that hypothyroidism, when the thyroid gland doesn’t make enough thyroid hormone, and elevated TSH levels were linked to a reduced risk of MS. By contrast, elevated FT4 was associated with an increased risk of MS.
However, further tests ruled out hypothyroidism and TSH as a cause of MS, while the relationship between elevated FT4 and MS risk remained causal.
Tests ruled out MS as cause of hypothyroidism, TSH changes
On the other hand, experiments on the causal effect of MS on thyroid function showed that MS reduced the risk of hypothyroidism and elevated TSH levels, but did not significantly affect FT4 levels. Still, tests ruled out MS as a cause of hypothyroidism and TSH changes.
The researchers then demonstrated that various immune cells with the protein markers CD27, CD28, CD19, CD33, or CD4 may mediate the causal association between thyroid function and MS. Moreover, genes in immune cells related to human leukocyte antigen (HLA), some of which are major risk factors for MS, played an essential role in the causal relationship between FT4 and MS.
In particular, FT4 mediated the effect of this relationship via HLA DR on immune cells with the protein marker CD33br, but not CD14, “suggesting that elevated FT4 levels may increase MS risk via this immune cell pathway,” the researchers wrote.
Conversely, FT4 exerted a reverse mediating effect through a subset of immune B-cells without the protein markers CD27 and immunoglobulin D, “indicating a potential protective role of this B cell subset against MS in the context of altered FT4 levels,” the researchers added.
“We have presented novel evidence suggesting that FT4 may serve as a causal determinant for the risk of developing MS,” the team concluded. These findings “imply an intricate interplay between MS and thyroid function, underscoring the necessity for further investigation to elucidate potential shared mechanisms underlying these two conditions.”
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