Immune system activity varies across MG subtypes, study finds

Different forms of myasthenia gravis (MG) may have distinct patterns of immune system activity, with MG that appears before age 50 and MG driven by antibodies against the muscle-specific kinase (MuSK) protein showing stronger activity, a study found.

“These findings underscore the immunological [variability] of MG and suggest that subgroup-specific immune mechanisms may contribute to disease [development],” the researchers wrote.

Data also suggested that age, type of self-reactive antibody, and the presence of a thymoma (a tumor in the thymus gland) are “key determinants of the immune response” in MG, they said.

The study, “Cytokine Profiles in Myasthenia Gravis Subgroups and the Lack of Any Effect of Immunosuppression,” was published in Muscle & Nerve by a team of researchers in Turkey.

Recommended Reading

July 20, 2026 Columns by Shawna Barnes

Being a caregiver with MG means keeping my distance

Different forms, different immune activity

MG is caused in most cases by self-reactive antibodies that mistakenly attack proteins involved in communication between nerves and muscles, resulting in MG symptoms such as muscle weakness and fatigue. Acetylcholine receptor (AChR) proteins are the most common target of MG-driving antibodies, followed by MuSK proteins.

Abnormalities in the thymus gland, a part of the immune system, are thought to contribute to MG, with about 15% of cases being linked to thymoma — referred to thymoma-associated MG (TAMG).

The disease can also differ by age of onset. Early-onset MG starts before age 50 and late-onset MG starts at age 50 or older. Juvenile MG is a form that starts before age 18.

Different forms of MG may vary in the extent to which the immune system is activated. To determine whether immune signaling proteins (cytokines) could help distinguish MG subtypes, the researchers analyzed blood samples from 87 adults with MG associated with antibodies against AChR or MuSK and from 25 healthy adults. Sixty-four percent were women.

All patients had generalized MG, a form of the disease that affects muscles throughout the body. Most (80.5%) tested positive for anti-AChR antibodies, while the remainder had MuSK-associated MG. Among those with AChR-related MG, 23 had late-onset disease, 22 had early-onset MG, and 25 had thymoma-associated MG.

Those with early-onset MG had significantly higher blood levels of several cytokines known to mainly drive inflammation, including IFN-gamma, TNF-alpha, and interleukin-2 (IL-2), IL-9, IL-17A, and IL-17F, compared with healthy adults. IL-37, IL-4, and IL-13 — cytokines known to also have anti-inflammatory or regulatory effects — were also found at significantly elevated levels in the early-onset MG group.

Compared with healthy controls, people with MuSK-related MG showed significantly higher levels of some of the same cytokines as the early-onset MG group. IL-6, a cytokine that has both pro-inflammatory and anti-inflammatory effects, was significantly elevated only in the MuSK-related MG group.

In late-onset MG patients, only IL-21, which helps immune B-cells produce antibodies, was significantly elevated relative to healthy adults. The remaining cytokines were found at levels comparable to those seen in healthy adults.

In people with thymoma-associated MG, only the pro-inflammatory cytokine IL-17A was significantly elevated compared with healthy controls, “indicating a predominance of Th17-driven immune mechanisms in TAMG [thymoma-associated MG],” the team wrote.

When the researchers compared the different forms of MG, they found that people with early-onset MG had significantly higher blood levels of IL-5, IL-6, IL-9, IL-17F, IFN-gamma, and IL-4 than those with late-onset MG, “indicating a heightened proinflammatory response,” the researchers wrote.

A similar pattern was found between MuSK-associated MG and late-onset MG.

Compared with thymoma-associated MG, early-onset MG was linked to higher levels of the pro-inflammatory cytokines IL-2 and IL-9 and the regulatory cytokines IL-4 and IL-13, while MuSK-associated MG was associated with higher levels of IFN-gamma and IL-4.

There were no significant differences between early-onset and MuSK-associated MG, suggesting shared cytokine patterns.

The researchers also created a heatmap, a color-coded chart that displays patterns across many measurements at once — in this case, levels of each cytokine measured. Statistical analyses based on this heatmap also grouped early-onset and MuSK-associated MG together because they showed similar cytokine patterns.

“In contrast, LOMG [late-onset MG] and TAMG patients displayed clustering patterns closer to healthy controls, suggesting relatively limited changes in their cytokine profiles,” the researchers wrote.

Many patients — all of those with early-onset or thymoma-associated MG and half of those with MuSK-related MG — had undergone thymectomy, a surgery to remove the thymus gland. All but four patients received immunosuppressive treatments (corticosteroids alone or with azathioprine).

Analyses of blood samples collected before and after treatment in the same patients showed no significant changes in cytokine levels, “suggesting a limited effect of treatment on [blood] cytokine profiles in MG patients,” the team wrote.

“In the present study, distinct cytokine profiles were identified across MG subgroups,” the researchers wrote, “separating [early-onset MG] and [MuSK-associated MG] from TAMG and LOMG with some similarities and highlighting the impact of age and thymoma presence on immune responses.”