Myagen

Autoimmunity results from aberrant immune responses directed not against pathogens, allergens, or tumors, but against the body itself.

Autoimmune diseases are frequent and are caused by autoreactive T cells and/or autoantibodies (auto-Abs). The human genetic and immunological causes leading to the breakdown of tolerance remain unknown for most autoimmune diseases.

Myasthenia gravis (MG) is an autoimmune disease where auto-Abs target the neuromuscular junction (AA-NMJ). In 2020, I found that auto-Abs neutralizing type I interferons (AAN-I-IFNs) are major, common, and global determinants of severe viral diseases. They are present before viral infection, and occur in the general population worldwide. Genetic etiologies of AAN-I-IFNs impair central thymic tolerance.

30% of MG patients harbor AAN-I-IFNs and MG patients can have thymic abnormalitie

I hypothesize that we can find genetic defects underlying MG.

The work proposed here aims to bridge current gaps in knowledge concerning the causes and mechanisms of human autoimmunity, by focusing on myasthenia gravis.

We will study:

• IThe clinical and thymic features of MG

• The immunological characteristics of MG

• The genetic causes of MG

Overall, I expect this study to generate new biological and medical insight into the pathogenesis of MG with the potential to alter diagnostic and therapeutic approaches to autoimmunity radically while revealing new basic biological mechanisms.