Thymectomy in children with myasthenia gravis: an option to consider

Among the results of a recent study on juvenile myasthenia gravis (JMG), we can cite that patients, particularly girls, could benefit from a thymectomy performed before puberty. The authors described their database-centric research in Scientific reports.¹

The team’s primary goal was to better characterize JMG, better understand the underlying etiological mechanisms of the disease, and hopefully help improve patients’ quality of life. They analyzed 85 pre- and 132 post-pubertal patients with MG, comparing them to 721 adults with MG aged 40 and younger.

The reason for examining pre- and postpubertal JMG separately is that pubertal changes may promote the development of autoimmune diseases.² The authors explained that since MG primarily affects females (and in each of their subgroups, females predominated, as would be expected), they set the threshold for puberty at 13, to match the first menstrual period, according to the Tanner scale.

They studied 40 years of clinical data, anti-acetylcholine receptor (AChR) antibody titers, thymectomy and thymic histology, and also performed a comprehensive review of the literature.

When specifically comparing prepubertal and postpubertal JMG, they found that the risk of developing MG was lower in the prepubertal group. However, they observed no significant difference between the 2 groups in female/male ratios; the percentages of patients in the JMG and adult MG groups who had anti-AChR titers and were AChR positive were also similar.

Postpubertal individuals with JMG have a higher degree of follicular hyperplasia, they found, and specifically, postpubertal females with JMG had the highest rates of lymphofollicular hyperplasia and germinal center (GC) grades. the highest. This is “likely exacerbated by elevated levels of female sex hormones…(as)…statistically significant results (suggest) a greater susceptibility of females to developing thymic follicular hyperplasia just after puberty,” the team noted.

Autoreactive AChR B cells emerge from the thymus, which plays an active role in their production, they continued. Furthermore, the degree of follicular hyperplasia and the amount of anti-AChR titer were correlated in JMG, and in all categories of patients, anti-AChR antibodies and GC grade were positively correlated.

Early ablation of the thymus could reduce the dispersion of autoreactive AChR B cells to the periphery. Thus, potentially, thymectomy before puberty would benefit patients with JMG, particularly in girls and especially if performed early in the course of the disease.

The data, however, revealed that the percentage of prepubertal patients who underwent thymectomy was significantly lower than that of other subgroups: 32.9% versus 42.5%. The time to thymectomy was also twice as long in the prepubertal group.

The authors’ literature review also revealed that in adult patients with MG, the number of GCs correlates with better postthymectomy outcomes, and that there is an inverse correlation between age at thymectomy and prevalence of GC in adult patients.

More biological details

Sex hormones play a crucial role in modulating the formation, function and maintenance of GCs in lymphoid tissues and in inflammatory conditions. “In GCs, the estrogen receptor α is expressed while the progesterone and androgen receptors are weakly or not expressed,” the authors explain. “Activation of the estrogen receptor α could promote the development of larger GCs.”

In contrast, they continued, higher serum levels of androgens apparently inhibit the development of thymic GCs in patients with MG. And, via their interactions with immune cells and cytokines, sex hormones influence the processes of B cell activation, antibody production and affinity maturation in pathological situations.

In an inflammatory environment such as that observed in the thymus of a patient with MG, “estrogens provide continued support for the activation of interferon signaling pathways, thereby increasing the progression of GC formation,” they write.

The references

1. Truffault F, Auger L, Dragin N et al. Comparison of juvenile and adult myasthenia gravis in a French cohort with a focus on thymic histology. Scientific representative 2024;14(1):13955. doi:10.1038/s41598-024-63162-0

2. Yang Q, Kennicott K, Zhu R et al. The influence of sex hormones on female autoimmune diseases suggests that puberty is an important factor in pathogenesis. Front Pediatrician. 2023;11:1051624. doi:10.3389/fped.2023.1051624