Letter on Multiple Acyl‐Coenzyme A Dehydrogenase Deficiency is Associated with Sertraline Use

Abstract

Regarding the second point raised, the immunohistochemistry analysis revealed MuSK expression in cancer cells of specimens from 2 different tumor types, which is a significant finding that cannot be overlooked. Specifically, we observed MuSK expression in primary mediastinal large B-cell lymphoma (PMBCL) and endometrial clear cell carcinoma (ECCC). These cancers are exceedingly rare, representing less than 5% of all uterine epithelial cancers and 3 to 10% of all diffuse large B-cell lymphomas, respectively. ICIs are currently administered only in refractory cases of these cancer subtypes.Importantly, ICI-induced toxicity is primarily driven by enhanced Th1 and Th17-associated responses. 4 In contrast, IgG4 production, the predominant isotype of MuSK antibodies, is induced by IL-4, IL-10, and IL-13, cytokines that are involved in a Th2-mediated immune responses. The predominance of Th1 and Th17 immune responses stimulated by ICIs, as opposed to a Th2-mediated immune response, likely explains why immune-related adverse events associated with ICIs are infrequently mediated by IgG4 autoantibodies. 5 Our findings provide insights in the potential role of MuSK in oncogenesis and suggest that MuSK-expressing cancer cells might act as a trigger for autoimmunity in certain patients. Further mechanistic studies are needed to validate these hypotheses and to deepen our understanding of the relationship between MuSK and cancer.