We found that PI3K/AKT-mediated downstream metabolic signaling molecules including pPI3K, pAKT, pmTOR, pS6, pFOXO1 had reduced activation in PBMCs of IgG4-RD patients compared to HCs (Fig. 5A, S9A), which was also consistent with the results in Usp25 KO B cells (Fig. S9B). Here, USP25 is linked to immunoglobulin G4-related sclerosing disease.