HLA-A*11:01 and HLA-C*03 Binding to FKBP1A Influences the Efficacy of Tacrolimus in Myasthenia Gravis Subgroups.

Tacrolimus (TAC) is recommended for the patients with drug tolerance or respond poorly to other conventional immunosuppressants in myasthenia gravis (MG), but its effectiveness is influenced by dose and genetic polymorphism. Studies suggest that HLA polymorphisms are significantly associated with susceptibility to MG, but the relationship between HLA and TAC efficacy in MG has not been explored. In this paper, we investigated the correlation between TAC therapeutic efficacy and HLA in different MG subgroups. HLA-C*03 was associated with a better response to TAC in patients with early-onset MG, generalized MG, and those with a high concentration of TAC. While HLA-A*11:01 showed poor responsiveness to TAC in generalized MG. Furthermore, computational docking was used to demonstrate the binding situation of HLA-A with the TAC binding protein FKBP1A. It showed that HLA-A*11:01 had a higher binding strength with FKBP1A than HLA-C*03, indicating that the combination of different types of HLA and FKBP1A may be one of the reasons affecting its therapeutic efficacy. This study highlights the influence of HLA on the efficacy of TAC among different MG subgroups, providing clues for precise treatment of MG with TAC.