Potential Link Found Between Obesity and Myasthenia Gravis Exacerbation

Having a higher body mass index (BMI) has been associated with having a higher risk of ocular myasthenia gravis, according to new study data from 940 patients living with the autoimmune neuromuscular disorder.¹

Publishing their findings in Orphanet Journal of Rare Diseases, the study authors explain that theirs is not the first investigation to propose such a connection. Previous analyses have suggested a similar correlation between obesity and chronic inflammation and between high BMI and autoimmune disease onset and severity.^2-5 Further, as with these results, the present authors highlight how potential obesity-induced increases in Th17 cells and decreases in T_reg cells signify an unbalanced immune reaction, and they propose that because of these changes, myasthenia gravis cases can worsen.¹

Patients recruited for the study had already been diagnosed with myasthenia gravis, but for the authors’ analysis, that diagnosis was confirmed through positive tests for anti–acetylcholine receptor (AChR) and anti–muscle-specific kinase autoantibodies, a positive test for neostigmine, which is a cholinesterase inhibitor used in the treatment of myasthenia gravis⁶; and abnormal repetitive nerve stimulation. The subtype of myasthenia gravis, ocular or generalized, was determined using Myasthenia Gravis Foundation of America (MGFA) criteria, and there were 2 classifications of BMI: low (< 24 kg/m²) and high (> 24 kg/m²).

Among the study population—whose age (IQR) was 50 years (34-62)—56% were in the low-BMI group, and most were female individuals (54.26%). The median disease duration and BMIs were 8.6 months (2.60-35.25) and 23.44 kg/m² (21.08-25.93). AChR antibodies of the immunoglobulin G class (AChR-IgG) were found 78.66%.

Far more patients had ocular myasthenia gravis compared with generalized disease (65.43% vs 41.60%), and of the 22.90% with thymoma, 29.66% underwent a thymectomy.

A Cox proportional hazards regression analysis that adjusted for age, sex, disease duration, MGFA classification, symptoms at onset, thymectomy, thymoma, AChR-IgG seropositivity, and immunotherapy, found a potential link between baseline BMI and risk of eventual generalized myasthenia gravis. | Image Credit: syahrir-stock.adobe.com

In the high-BMI cohort, patients were older (55 vs 44 years; P < .001), male (58% vs 42% female; P < .001), and had a significantly shorter median disease length (6.40 [2.48-26.98] vs 10.70 [2.88-37.20] years; P = .014). This group also had a higher rate of ocular disease at onset (71.88% vs 60.31%; P < .001), overall ocular disease classification (47.36% vs 37.02%; P = .001), AChR-IgG seropositivity (83.24% vs 75.11%; P = .007), and lower incidence of thymectomy (25.31% vs 33.09%; P = .027). Baseline median Activities of Daily Living (ADL) scores were close to equal, at 3 (2-6) in the low-BMI group and 3 (2-5) in the high-BMI group.

Unfortunately, 21.9% of patients were lost to follow-up. However, of the remaining 734 patients who were followed over a median of 33 months (26-39), 75.2% received immunotherapy, as did more patients with a low vs a high BMI (P = .015). Also, fewer patients in the low-BMI group whose initial diagnosis was ocular myasthenia gravis progressed to generalized myasthenia gravis compared with the high-BMI group (P = .036).

Minimal symptom expression rates (P = .677) and proportions of ADL responders (P = .632), for those whose baseline ASL score was 5 or higher, were similar between the cohorts.

A Cox proportional hazards regression analysis that adjusted for age, sex, disease duration, MGFA classification, symptoms at onset, thymectomy, thymoma, AChR-IgG seropositivity, and immunotherapy found a potential link between baseline BMI and risk of eventual generalized myasthenia gravis (HR, 1.06; 95% CI, 1.01-1.11; P = .026). Further, each added 1 kg/m² pushed the risk 6% higher. Baseline BMI was not linked to ADL response (P = .240).

Because the global obesity rate has seen such immense growth in recent decades, “exploring the relationship between BMI and health is of great importance,” the authors wrote. They explain that their findings also echo research that has found higher levels of pro-inflammatory and autoreactive antibodies in obesity, “likely due to CD40L signaling that enhances the production of inflammatory cytokines in adipocytes”—suggesting that weight loss could benefit persons with obesity and myasthenia gravis.

Still, they also highlighted limitations to their findings, including that they did not collect data on exact dosages and timing of nonglucocorticoid immunotherapy, only measured BMI at baseline, did not measure body composition beyond BMI, and the potential for missed diagnoses.

References

1. Chen HX, Wang ZY, Zhang NN, et al. Impact of body mass index on clinical presentation and prognosis in myasthenia gravis. Orphanet J Rare Dis. 2025;20(1):361. doi:10.1186/s13023-025-03902-1
2. 2. Winer S, Paltser G, Chan Y, et al. Obesity predisposes to Th17 bias. Eur J Immunol. 2009;39(9):2629-2635. doi:10.1002/eji.200838893
3. 3. Tsigalou C, Vallianou N, Dalamaga M. Autoantibody production in obesity: is there evidence for a link between obesity and autoimmunity? Curr Obes Rep. 2020;9(3):245-254. doi:10.1007/s13679-020-00397-8
4. 4. Luo W, Wang X, Kong L, Chen H, Shi Z, Zhou H. Initial BMI effects on clinical presentation and prognosis in neuromyelitis optica spectrum disorder. Ann Clin Transl Neurol. 2023;10(9):1673-1681. doi:10.1002/acn3.51857
5. 5. Harpsøe MC, Basit S, Andersson M, et al. Body mass index and risk of autoimmune diseases: a study within the Danish National birth cohort. Int J Epidemiol. 2014;43(3):843-855. doi:10.1093/ije/dyu045
6. Neostigmine. Drugbank. July 8, 2007. Accessed July 15, 2025. https://go.drugbank.com/drugs/DB01400