High levels of immune protein linked to MG severity, relapse risk

Immune protein MIF may is possible biomarker of disease activity

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A dropper hovers next to four vials of blood.

Higher levels of an immune protein called macrophage migration inhibitory factor (MIF) in the blood are linked to more severe myasthenia gravis (MG) and an increased risk of relapse, according to a study.

The findings suggest MIF could be used as a biomarker of MG disease activity, the study’s researchers said in “Macrophage migration inhibitory factor: A noval biomarker upregulates in myasthenia gravis and correlates with disease severity and relapse,” which was published in Cytokine.

MG occurs when the immune system produces self-reactive antibodies that interfere with nerve-cell communication, causing muscle weakness and fatigue, among other symptoms. Antibodies are produced by B-cells, a type of immune cell.

In autoimmune diseases like lupus and rheumatoid arthritis, high levels of MIF are linked to inflammation and damage. When the immune system detects a threat, MIF is released into the bloodstream not just by T-cells, as initially thought, but also by other immune cells such as B-cells.

“MIF can be a new promising therapeutic target for autoimmune diseases or even refractory autoimmune diseases [those that fail to respond to available medications],” the researchers wrote.

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MIF and MG severity, relapse risk

Researchers in China examined the relationship between MIF levels in the blood and MG severity and relapse — defined as new or worsening symptoms that last more than a day — to learn more about the role of MIF in MG. The study included 145 people with MG. From these, 79 had new-onset disease, 30 were in remission, meaning they had no symptoms, and 36 had relapsed. More than half were women.

Nearly half (46.8%) of those with new-onset disease had ocular MG, a form of the disease confined to the muscles that control the eye and eyelid movements, whereas 42 (53.2%) had generalized MG, a more severe form of the disease where muscle weakness and fatigue are widespread.

Median blood levels of MIF were significantly higher in people with new-onset MG than in 48 people without MG who were included as controls (195.28 vs. 78.71 picograms per milliliter, or pg/mL).

They also were significantly higher in people with generalized MG than with ocular MG (251.49 vs. 162.65 pg/mL), and in people with moderate or severe muscle weakness than in those with mild or no muscle weakness (272.83 vs. 175.47 pg/mL).

Higher levels of MIF in the bloodstream were linked to higher quantitative MG (QMG) scores, a measure of disease severity where higher scores indicate more severe disease.

Moreover, higher blood levels of MIF were linked to higher MG Foundation of America (MGFA) classes, indicating more severe clinical presentation, and a higher number of memory B-cells, a type of long-lived B-cell that can produce antibodies faster and more efficiently.

The researchers also looked for differences between 18 people with new-onset disease and 18 in remission, finding as the disease enters remission, blood levels of MIF and B-cell numbers decrease.

The presence of a thymoma, a tumor that forms in the thymus gland and may drive MG, was a risk factor for relapse in generalized MG. Rituximab, an antibody-based therapy that works by depleting B-cells, worked well in preventing a relapse.

High blood levels of MIF also were identified as a risk factor for relapse in patients with generalized MG. Using a cutoff value of 163.94 pg/mL, blood MIF levels correctly identified who with generalized MG went on to have a relapse in 63.9% of the cases and correctly ruled it out in 96.7%.

The findings suggest “MIF can be used as a novel biomarker to reflect disease severity and predict disease relapse in MG patients,” wrote the researchers, who noted that, while the exact role of the immune protein remains unclear, “MIF may play a key role in controlling the autoimmune responses in MG pathogenesis [disease mechanisms].”