Blood: MTOR activation enhancement for iexclusiveithasic multicenter Castleman disease

Iblast multicenter Castleman disease (iMCD) is a rare and incomprehensible blood disease characterized by lymph node disease, systemic inflammation, decreased blood cells, and multi-organ dysfunction in lifeInterleukin 6 (IL-6) inhibition can be effective in treating about 1/3 of patientsDue to the lack of clarity of etiology, the type of anadage and signaling pathways, the choice of il-6 nonresponders is limitedArenas et alhave reported three cases of mTOR activation-enhanced anti-IL-6 non-responders who respondtoto to siromos inhibition mTORIn this study, Arenas et alstudied mTOR signals from iMCD patients and control tissues and serum protein groupstested for pS6, p4EBP1 and p70S6K (known as mTORC1-activated effect molecules and indicators) in the lymph nodes of iMCD patients (26 cases) and controlled by immunohistomy (IHC) through immunohistization (IHC), the results showed an increase in mTOR activation in the small foam gap between the lymph nodes of iMCD patients compared to the healthy controlIn addition, IHC tests pS6 showed that iMCD's mTOR activation was higher than that of Hodgkin's lymphoma, systemic lupus erythematosus and reactive lymph nodes, suggesting that mTOR activation in iMCD was not only a product of lymphatic/inflammatory lymph node diseasein addition, the activation of mTOR in iMCD is comparable to that of autoimmune lymphatic tissue hyperplasia syndrome, a disease caused by hyperactivation of mTOR that responds to the treatment of siromosgene enrichment analysis of serum proteomic data in iMCD patients (88 cases) and control (42 cases) showed significant lyathing in mTORC1 signalFinally, functional studies showed an increase in the activation of the baseline mTOR pathway stoma in patients with iMCD remission compared to healthy controlsIL-6 stimulation enhances mTOR activation in iMCD patients, which can be offset by JAK1/2 inhibition, this study shows that mTOR activation can be used as a new therapeutic target for iMCD patients (now studied through the siromos trial)