单细胞测序分析揭示浆细胞异常激活及细胞毒性功能缺陷的免疫特征OA

Objective:To further explore pathogenesis of Kawasaki disease(KD),and to explore immune profile of patients with KD by single-cell RNA sequencing(scRNA-seq),providing promising targets for treatment of KD.Methods:Based on GSE168732 dataset,performing scRNA-seq analysis to identify cell subtypes and differentially expressed genes(DEGs)in 3 KD pa-tients and 3 healthy controls,and validated results in serological test results of 22 KD patients and 44 healthy controls.Results:Com-pared with healthy controls,proportion of CD19+plasma cells in KD patients was significantly increased,while proportion of cytotoxic immune cells(CD56dimCD16+_NK cell subset and effector LAG3+CD8+_T cell subset)were significantly reduced in KD group.Clinical serological tests similarly revealed that compared with matched controls,KD patients exhibited a significantly higher proportion of B cells(P<0.001),while conversely showing significantly lower NK cell counts(P=0.023)and a reduced percentage of CD3⁺T cells(P=0.036).In addition,cytotoxicity-related activating receptors(KLRD1,KLRC3)and cytotoxicity effector molecules(PRF1,NKG7,etc.)were down-regulated in KD group compared with healthy control group.Clinical inflammatory cytokine panel analysis demonstrated significantly elevated IL-6 levels in KD patients'peripheral blood compared to controls(P=0.018),accompanied by significantly reduced IFN-α levels(P=0.028).Activated platelet(PLT)specific marker genes(PTCRA,FOLR3,etc.)were identified in C6_plasma cell subset.Proportion of C6_plasma cell subset was increased in KD group compared with healthy control group.Further subgroup analysis based on PLT levels revealed that KD patients with abnormally elevated PLT demonstrated a trend toward higher B-cell propor-tions(P=0.099)and significantly reduced NK-cell percentages(P=0.005)compared to normal PLT.Conclusion:There are increased proportion and dysfunction of plasma cells in KD,concurrently with reduced proportions of cytotoxic immune cells.Specific plasma cell subset may contribute to aberrant PLT activation,representing significant risk factors for KD progression,providing promising targets and a laboratory foundation for new therapeutic strategies of KD.