Calprotectin, Inflammatory Protein, May Be Biomarker of MG Severity

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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An inflammation-associated protein called calprotectin is present at abnormally high levels in the blood of people with myasthenia gravis (MG), a new study reports.

Data also suggest that levels of this protein might correlate with MG activity and severity, but further investigation is needed, according to its researchers.

“There is an urgent need for a sensitive biomarker in MG that reliably predicts the individual disease course and exacerbation, as well as guiding immune suppressive treatment, especially in the light of emerging and more specific therapy options for MG patients,” they wrote.

The study, “Calprotectin as potential novel biomarker in myasthenia gravis,” was published in the Journal of Translational Autoimmunity.

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Calprotectin is a signaling protein that specific types of immune cells release to coordinate inflammation and prevent bacterial growth. Prior research suggests that calprotectin levels are associated with disease activity in people with inflammatory bowel disease (IBD), an autoimmune disease of the digestive tract.

A team of researchers in Germany tested whether measuring calprotectin levels might be useful in assessing disease activity and severity in people with MG, an autoimmune disease that affects the connections between nerve and muscle cells.

Researchers measured and compared calprotectin levels in the serum — the liquid part of blood — of 251 people with MG, 77 healthy controls, and 13 people with non-inflammatory neurological diseases (polyneuropathies, disorders marked by damage to peripheral nerves).

Demographics were similar across groups. MG patients had a mean age of 54.4, and more than half (59%) were female. Most MG patients were on corticosteroids or other immune-suppressing medications, and just over half had undergone a thymectomy, a surgical procedure to remove the thymus gland.

Mean serum calprotectin level in MG patients was 4.3 micrograms per milliliter (mcg/mL) — significantly higher than that seen in healthy controls (2.1 mcg/mL) and in people with non-inflammatory neurological diseases (2.0 mcg/mL).

Among MG patients, these levels were not significantly associated with age, gender, MG type, or types of MG-associated autoantibodies. There were also no significant associations between calprotectin levels and the use of certain MG medications or a history of thymectomy.

The fact that calprotectin levels were elevated in MG patients, but not in people with non-inflammatory neurological diseases, might make calprotectin useful for differentiating MG from other conditions, the researchers noted.

“This explorative cross-sectional and prospective study demonstrates that CLP [calprotectin] levels were significantly higher in MG compared to controls,” the team wrote.

Statistical analyses also showed these levels tended to be higher in patients with generalized MG, compared with those with purely ocular disease or patients in remission. There was also a weak, but statistically significant, correlation between serum calprotectin levels and the quantitative myasthenia gravis (QMG) score, a measure of disease severity.

Researchers also assessed calprotectin levels over the course of three years in 58 MG patients to see whether they changed in accordance with clinical changes in disease severity. They found little evidence suggesting such a link, but noted findings here could have been affected by treatments being used by most of these people and an “unclear … precise cut-off value” in disease severity score measures.

“Baseline CLP levels correlated weakly, but positively with clinical disease activity as measured by QMG score and [MG type and status],” the researchers concluded.

“Further multicentric, longitudinal investigations are strongly needed to determine the potential utility of CLP as a biomarker for better care of patients with MG,” they added.