IL-41 may be potential biomarker as levels correlate with MG severity

Levels decreased when symptoms steadily improved with treatment: Study

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by Andrea Lobo |

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Blood levels of interleukin-41 (IL-41) — a signaling molecule involved in immune responses — are found to be significantly elevated in people with myasthenia gravis (MG), and associated with disease severity and inflammatory markers, a study from China reports.

These findings indicate “IL-41 may be essential to the [disease] mechanism of MG and a potential biomarker for MG,” according to researchers.

The study, “Increased serum interleukin-41 correlates with disease severity in myasthenia gravis,” was published in the journal International Immunopharmacology.

MG is an autoimmune condition driven by self-reactive antibodies that target and attack proteins involved in nerve-muscle communication, most commonly acetylcholine receptors (AChRs). Impairments in nerve-muscle communication lead to the hallmark symptoms of muscle weakness and fatigue that characterize MG and that can affect the patient’s ability to see, swallow, speak, or walk.

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IL-41 is signaling molecule involved in inflammation, autoimmune responses

IL-41 is a signaling molecule involved in inflammation and autoimmune responses, and has been found to be associated with several immune diseases. It has also been shown to increase the expression, or production, of other signaling proteins involved in MG-related mechanisms.

“However, the relationship between IL-41 and MG is still unknown,” the researchers wrote.

To know more about the correlation between the level of IL-41 in the blood and MG clinical signs, as well as its association with inflammation and immune indicators, researchers in China analyzed data from 60 MG patients and 30 healthy controls.

Patients were a mean age of 54.4 years and more than half were men (55%). All had anti-AChR antibodies, and the majority had generalized MG (43 patients) — a more severe disease form characterized by widespread muscle weakness involving several muscle groups. The remaining 17 had ocular MG, a form of the disease that primarily affects the muscles controlling eye and eyelid movements.

IL-41 levels in the blood were significantly higher in MG patients than in healthy participants (82.09 vs. 77.09 picograms per milliliter, pg/mL). No differences in IL-41 levels were found between men and women, or between patients with different types of MG. Similarly, no differences in IL-41 levels were found between patients with early-onset MG and late-onset disease.

However, there were differences in disease severity. Specifically, patients with moderate or severe generalized weakness, according to the MG Foundation of America (MGFA) score, had significantly higher levels of IL-41 than those with ocular MG or mild generalized weakness (88.4 vs. 79.2 pg/mL).

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IL-41 levels correlated with disease severity, inflammatory markers

The researchers also found IL-41 levels in the blood were positively correlated with measures of disease severity (MGFA and MG Activities of Daily Living scores), as well as with inflammatory markers.

When looking at patients who had been treated with Vyvgart (efgartigimod alfa-fcab), the researchers found IL-41 levels increased during the first cycle of treatment. However, from the time of disease onset, IL-41 levels significantly decreased as clinical features improved (78.3 vs. 73.4 pg/mL).

Finally, the area under the curve (AUC) was calculated for IL-41. This type of statistical analysis yields values between 0 and 1, with higher numbers indicating a greater diagnostic accuracy of IL-41 at distinguishing MG patients from controls. In this analysis, IL-41 had an AUC value of 0.63, indicating it may hold diagnostic value for MG.

“Our results showed that IL-41 was markedly elevated in MG patients and significantly associated with disease severity as well as inflammatory markers … while [it decreased] when clinical features steadily improved, suggesting that IL-41 was a valuable biomarker for MG,” the researchers wrote.

“In the future, a more in-depth understanding of the specific mechanism of IL-41 in MG is worth further research to better understand the [disease mechanisms] of MG and develop new therapeutic strategies,” they added.