Blood T-cell marker may help flag MG recurrence after thymectomy

Measuring the percentage of CD3-positive T cells in the blood after thymectomy, or surgical removal of the thymus, may help identify recurrence risk in people with myasthenia gravis (MG) who do not have a thymoma, or thymus tumor, a study suggests.

Data from 275 patients showed that those with a higher percentage of CD3-positive T cells after surgery had significantly lower odds of recurrence — 43% lower after adjustment — than those with a lower percentage.

“These findings suggest that postoperative [CD3-positive] T-cell percentage may be a clinically accessible marker associated with recurrence risk, but external validation and prospective studies are needed,” the researchers wrote.

The study, “Association between postoperative peripheral blood CD3+ T-cell percentage and recurrence after thymectomy in non-thymomatous myasthenia gravis: a retrospective cohort study,” was published in the journal Neuromuscular Disorders.

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How the thymus may influence MG

MG is caused by self-reactive antibodies that target proteins involved in nerve-muscle communication, most commonly acetylcholine receptors (AChRs). This disrupts signaling between nerves and muscles, causing symptoms that include muscle weakness and fatigue.

The thymus, an organ in the chest where immune T cells mature, is thought to be involved in the abnormal immune responses that underlie MG. T cells help regulate other immune cells, including B cells, which produce antibodies.

A thymectomy is recommended for MG patients with a thymus tumor, called a thymoma, and selected people with generalized MG who test positive for anti-AChR antibodies and do not have a thymoma. Generalized MG is marked by symptoms affecting several muscle groups across the body.

The MGTX clinical trial and its extended follow-up showed that thymectomy plus the corticosteroid prednisone improved clinical outcomes compared with prednisone alone in MG patients without a thymoma, with benefits persisting during extended follow-up.

Still, outcomes after thymectomy vary, and some people experience a return or worsening of MG symptoms. Identifying an accessible marker associated with recurrence risk could help guide follow-up care.

CD3 is a protein found on mature T cells, and the percentage of CD3-positive T cells in the blood provides a broad measure of circulating T-cell status. Earlier studies suggest thymectomy may alter T-cell populations, but whether postoperative CD3-positive T-cell percentages are linked to longer-term MG recurrence risk has remained unclear.

To fill this knowledge gap, researchers retrospectively analyzed data from 275 people with MG and no thymoma who underwent thymectomy between 2020 and 2023. All patients in the final analysis were treated at a single hospital in China.

Participants’ median age at MG onset was 37 years, and 52.7% were women. Nearly all patients (97.5%) were positive for anti-AChR antibodies, and the median time from MG onset to thymectomy was 16 months. Among the 194 patients with available timing data, CD3-positive T-cell measurements were obtained a median of 12 months after surgery.

The median postoperative CD3-positive T-cell percentage was 77.3%. The 136 people with values below the median were included in the low CD3T group, while the 139 people with values at or above 77.3% comprised the high CD3T group.

Higher CD3T linked to fewer recurrences

Compared with the low CD3T group, the high CD3T group had a significantly longer median time from MG onset to thymectomy (20 vs. 12 months), significantly higher rates of pre-surgery immunotherapy (60.4% vs. 44.1%), and a shorter median follow-up after thymectomy (30 vs. 42 months).

After surgery, 82 patients experienced recurrence, which was defined as the reappearance of MG symptoms after thymectomy or worsening of symptoms during follow-up. Recurrence occurred in 36% of patients in the low CD3T group and 23.7% of those in the high CD3T group, a difference that was statistically significant.

After adjusting for age at MG onset, sex, preoperative disease severity, time from MG onset to thymectomy, and preoperative immunotherapy, the high CD3T group had significantly lower odds of recurrence — 43% lower than the low CD3T group. A separate time-to-event analysis showed the same direction, but the association did not reach statistical significance.

However, “biological interpretation of this association should be cautious,” the researchers wrote, as the findings do not prove that a higher percentage of CD3-positive T cells directly protects against recurrence.

The CD3-positive T-cell percentage captures the overall share of circulating T cells but cannot distinguish among T-cell subtypes, which have different roles in immune responses.

“One possible explanation is that a higher postoperative [CD3-positive] T-cell percentage may reflect a more preserved or rebalanced [circulating] T-cell compartment after thymectomy,” the researchers wrote. “Another possibility is that a lower value may indicate more intensive immunotherapy, [body-wide] immune suppression, infection, disease activity, or other unmeasured clinical factors.”

Studies that follow patients over time and use standardized monitoring of immune cells and T-cell subsets are needed to clarify the mechanisms behind the observed association, the team noted.

Because CD3-positive T-cell percentage can be measured using routinely available blood immune-cell testing, validating the marker could support its use as one part of a broader postoperative assessment to identify people with MG who may need closer monitoring after thymectomy, the researchers concluded.