Differentiating between idiopathic and immune checkpoint inhibitor-induced (ICI) myasthenia gravis (MG) may be more challenging than initially thought, according to a study recently published in Annals of Clinical and Translational Neurology.
“The contrasting properties of AChR autoantibodies in these cases challenge the accuracy of serological testing in establishing definite ICI-MG diagnoses and underscore the importance of a thorough clinical assessment when evaluating ICI-related adverse events,” the authors wrote.
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This retrospective, multicenter case series included 5 patients previously diagnosed with ICI-MG. Median age of symptom onset was 71 years. Only 1 was a female. On the other hand, the control group consisted of 32 patients with idiopathic MG and 2 OCI-MG.
Among the ICI-MG group, the most frequent neoplasms were renal cell carcinoma and prostate cancer, present in 2 different patients, followed by 1 patient with thymoma. Most patients received more than 3 cycles of chemotherapy before the onset of MG. The most common class of MG Foundation of America (MGFA) was IIIB in 3 patients, while only 1 was class I and 1 class IVA.
Some individuals from the ICI-MG (60%) and OCI-MG (50%) tested positive for acetylcholine receptor (AChR) autoantibodies, and only 1 with ICI-MG exhibited complement fixation in vitro. Epitope mapping revealed polyclonal autoimmune activity towards various AChR subunits in the same patient. Interestingly, no other AChR autoantibody-positive patients with ICI-MG showcased a similar pattern. Moreover, ICI-MG and OCI-MG patients did not test positive for LRP4 autoantibodies.
These results demonstrate that AChR autoantibodies among ICI-MG patients do not possess pathogenic effector activity in vitro, further proposing that other factors from the humoral and cellular immunologic system could play a more fundamental role in this MG subtype.
“Translated into clinical practice, these findings challenge the accuracy of serological testing alone in establishing a definite ICI-MG diagnosis and corroborate the need for more in-depth ancillary investigations when evaluating muscle-related irAEs,” the authors concluded.
Masi G, Pham M, Karatz T, et al. Clinicoserological insights into patients with immune checkpoint inhibitor-induced myasthenia gravis. Ann Clin Transl Neurol. Published online March 3, 2023. doi:10.1002/acn3.51761