HLA in myasthenia gravis: From superficial correlation to underlying mechanism

Myasthenia gravis (MG) is a rare autoimmune disease characterized by muscle weakness and abnormal fatigability. Like many other autoimmune diseases, genetic contribution to MG has been studied where the HLA system appears to play the most vital role. Although many correlations have been revealed in these studies, the underlying mechanism for them is still in the veil. Based on current evidence, we propose two synergetic mechanisms underlying the MG predisposition via HLA. In brief, the first advocates specific MHC II-peptide patterns that influence the efficacy of antigen presentation, and the second emphasizes the role of classical MHC alleles in shaping the TCR repertoire for MG predisposition. Besides, possible explanations for unresolved or controversial MG-related epidemiological phenomenon or clinical problems are addressed as well. Then, we discuss three factors influencing the effect of HLA on MG: gender discrepancy, inflammatory microenvironment, and epigenetic regulation. Lastly, from a provisional angle, we introduce several precautious treatments for people highly predisposed to MG. Although this is a review focusing on MG, the underlying mechanisms might be applicable in other autoimmune diseases as well.