Immune cell types may predict recovery in MG, study finds
Patients who recover have higher numbers of certain monocyte subsets
People who recover from myasthenia gravis (MG) after long-term treatment have higher numbers of certain subsets of monocytes — a type of immune cell — and lower numbers of others, a small study in China found.
“Consistent with previous studies, our study further validated that dysregulation of immune cells, especially monocytes, is likely to contribute to MG development,” the researchers wrote. “These findings provide new evidence for the development of therapeutic strategies and propose potential biomarkers for assessing treatment efficacy and prognosis for patients with MG.”
The study, “Single-cell RNA sequencing reveals cell immune status and dysregulated monocytes in patients with myasthenia gravis,” was published in Clinical & Translational Immunology.
MG occurs when self-reactive antibodies disrupt normal communication between nerve and muscle cells, causing muscle weakness that worsens with activity. While treatment may ease MG symptoms, some patients do not respond well and others see their symptoms return.
The researchers set out to look for biomarkers that may signal functional cure in MG — that is, when the disease is stable or results in no symptoms.
Data show ‘dynamic changes’ in cell profiles
The scientists analyzed the number and activity of immune cells in blood samples from four people newly diagnosed with MG. The samples were collected before treatment, one month after treatment, and six months to one year after treatment.
Treatment included the corticosteroid methylprednisolone and pyridostigmine bromide, an approved MG-therapy sold as Mestinon, with generics available.
The analyses detected 14 major immune cell types, including neutrophils, monocytes, T-cells, natural killer (NK) cells, and B-cells.
In blood samples collected more than six months after starting treatment, when MG was stable or symptoms had disappeared, the relative percentage of neutrophils was reduced. Meanwhile, the percentage of monocytes, NK cells, and a specific subset of T-cells was increased, compared with samples both before treatment and one month after treatment.
“These data revealed the dynamic changes of immune cell profiles among individuals” before, one month after, and six to 12 months after treatment, the team wrote.
For further analysis, the researchers focused on monocytes, a type of immune cell that circulates in the bloodstream and is a major component of the general immune response to inflammation. A total of nine monocyte subtypes were identified in the patients’ samples.
Samples from people who had recovered from MG showed a significant expansion of two monocyte subtypes — called CD14-positive and CD14- and S100A12-positive — and a significant depletion of another monocyte subtype, called CD14- and FOS-positive, relative to samples collected in the other two time points.
CD14 is a protein receptor that recognizes bacteria and is mainly found in monocytes. The S100A12 protein “is considered a crucial factor in inflammation and is related to inflammatory processes in autoimmune disorders,” the researchers wrote, adding that S100A12 levels have been reported to be increased in people with MG.
“The functional mechanism of S100A12 in MG requires further investigation,” the team wrote.
The FOS protein is part of a protein complex involved in the regulation of gene activity, and its presence suggests a recently activated monocyte. A previous study reported low FOS in MG patients after traditional Chinese medicine treatment.
“Consistent with [these] results, we observed the depletion of CD14- and FOS-positive monocytes in the [functional cure] group, demonstrating the key role of FOS in MG therapy,” the researchers wrote.
Levels of inflammation were also significantly different across the three time points.
“Our study identified two dysregulated monocytes, elucidated inflammation status, and provided insights on understanding the [cause] of functional cure in patients with MG,” the team wrote.
They added that monitoring the numbers of these monocyte subsets may be useful for understanding when a patient has reached a functional cure, and could help develop better treatments for MG.
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