Clinical features and HLA typing of immune checkpoint inhibitor-associated myasthenia gravis, myocarditis and myositis

Background: Immune checkpoint inhibitors (ICI) have significantly improved the therapeutic outcomes for various malignant tumors, but they may also trigger severe immune-related adverse events (irAEs), such as myositis, myocarditis and myasthenia gravis (MG). The mechanisms underlying these adverse reactions remain unclear and may be related to an individual's genetic background. Human Leucocyte Antigen (HLA) genes play a crucial role in immune regulation, and their polymorphism is closely related to the occurrence of various autoimmune diseases. Method: To clarify whether irAEs is associated with specific HLA typing, we analyzed 23 patients diagnosed with myositis, myocarditis and/or MG after receiving ICI therapy, and conducted HLA high-resolution typing detection using the PCR-SBT method. Results: Among the 14 patients with MG combined with myositis and myocarditis, the frequencies ofHLA-DQB1*03:03 and HLA-C*01:02 loci were higher than those in the normal population. In 9 patients with myositis and myocarditis, the frequency of HLA-B*52:01 locus was higher than that in the normal population. Conclusion: Our research findings reveal that patients carrying autoimmune susceptibility genes have a higher risk of developing irAEs when treated with ICI, specific HLA alleles may be associated with the risk of ICI-related MG/myositis/myocarditis, but further large-scale, multi-center validation is needed.