IgG4-related disease (IgG4-RD) is a newly recognized systemic autoimmune disease that can involve the pan- creatobiliary tract, retroperitoneum/aorta, head and neck region, and salivary glands, et al. IgG4-RD is characterized by elevated serum IgG4 levels, tumefactive lesions with a dense lymphoplasmacytic infiltration rich in IgG4 positive plasma cells and storiform fibrosis of related organs.~Glucocorticoids are the first-line agents for the treatment of IgG4-RD, however, in order to maintain long-term disease stability and avoid disease relapse, glucocorticoids maintenance therapy should last for a long period, which may induce various glucocorticoid-associated adverse reactions. For some mild IgG4-RD patients without internal organ damage, long-term glucocorticoids therapy may have a low benefit/risk ratio. Further, a substantial proportion of patients cannot tolerate glucocorticoids.~Sirolimus, also known as rapamycin, is a macrolide compound that inhibits its mechanistic target (mTOR), which regulates cell growth and metabolism in response to environmental cues. mTOR is also essential in driving abnormal lineage specification within the immune system in various rheumatic diseases. We discovered that mTOR was highly activated in IgG4RD tissues, and its inhibitor sirolimus appeared as a good treatment candidate.
gG4-related disease (IgG4-RD) is a newly recognized systemic autoimmune disease that can involve the pan-creatobiliary tract, retroperitoneum/aorta, head and neck region, and salivary glands, et al. Glucocorticoids are the first-line agents for the treatment of IgG4-RD, however, in order to maintain long-term disease stability and avoid disease relapse, glucocorticoids maintenance therapy should last for a long period, which may induce various glucocorticoid-associated adverse reactions. Sirolimus plays dual roles in inhibiting lymphocyte activation and fibroblast proliferation. It is inferred from its mechanism that sirolimus is a good potential treatment option for IgG4-RD. Therefore, we conducted this single-arm clinical trial on patients with IgG4-RD to determine the efficacy and safety of sirolimus.