부산대학교 도서관

BACKGROUND. Macrophage activation syndrome (MAS) is a life-threatening complication of Still's disease (SD) characterized by overt immune cell activation and cytokine storm. We aimed to further understand the immunologic landscape of SD and MAS. METHOD. We profiled PBMCs from people in a healthy control group and patients with SD with or without MAS using bulk RNA-Seq and single-cell RNA-Seq (scRNA-Seq). We validated and expanded the findings by mass cytometry, flow cytometry, and in vitro studies. RESULTS. Bulk RNA-Seq of PBMCs from patients with SD-associated MAS revealed strong expression of genes associated with type I interferon (IFN-I) signaling and cell proliferation, in addition to the expected IFN-[gamma] signal, compared with people in the healthy control group and patients with SD without MAS. scRNA-Seq analysis of more than 65,000 total PBMCs confirmed IFN-I and IFN-[gamma] signatures and localized the cell proliferation signature to cycling [CD38.sup.+][HLA-DR.sup.+] cells within [CD4.sup.+] T cell, [CD8.sup.+] T cell, and NK cell populations. [CD38.sup.+][HLA-DR.sup.+] lymphocytes exhibited prominent IFN-[gamma] production, glycolysis, and mTOR signaling. Cell-cell interaction modeling suggested a network linking [CD38.sup.+][HLA- DR.sup.+] lymphocytes with monocytes through IFN-[gamma] signaling. Notably, the expansion of [CD38.sup.+][HLA-DR.sup.+] lymphocytes in MAS was greaterthan in other systemic inflammatory conditions in children. In vitro stimulation of PBMCs demonstrated that IFN-I and IL-15--both elevated in MAS patients - synergistically augmented the generation of [CD38.sup.+][HLA- DR.sup.+] lymphocytes, while Janus kinase inhibition mitigated this response. CONCLUSION. MAS associated with SD is characterized by overproduction of IFN-I, which may act in synergy with IL-15 to generate [CD38.sup.+][HLA-DR.sup.+] cycling lymphocytes that produce IFN-[gamma].
Introduction Still's disease (SD) is characterized by recurrent fever, skin rash, arthritis, and systemic inflammation. SD was first recognized in children and is commonly called systemic juvenile idiopathic arthritis (sJIA) [...]