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关键词： ST2L   cytotoxic T cells   epidermal necrolysis   interleukin-33   perforin  

关键词： bimekizumab   interleukin-17 inhibitors   palmoplantar psoriasis   refractory psoriasis   skin of color   IL   interleukin  

摘要： Marked improvement in the same patient’s palms after 4 weeks of treatment with bimekizumab, demonstrating near-complete resolution of plaques. Introduction Palmoplantar psoriasis is a localized form of psoriasis primarily affecting the palms and s...

关键词： CD8   T cells   Lupus   IL7 receptor   Neutrophils  

摘要： Background This study aims to interrogate the implications of CD8 + T cells in lupus by examining CD8 + T cell heterogeneity and assessing the significance of this heterogeneity in promoting inflammation and tissue damage. Methods Our own and publicly available RNA-seq and microarray data from the peripheral blood and kidney tissues of patients with lupus were analysed. Imaging Mass Cytometry (IMC) analysis of immune cells was conducted in lupus and normal kidney tissues. The effects of CD8 + T cell subsets on neutrophils were evaluated ex vivo . Findings Our scRNA-seq analysis showed an accumulation of effector memory (EM) CD8 + T cell subsets that expressed low levels of the IL7 receptor gene (IL7R low ) but high levels of effector molecule genes, including GZMB , GZMK , PRF1 , and GNLY , in the peripheral blood and kidneys of patients with lupus. CD8 + T cell infiltrations and cytotoxic molecule expression in lupus kidney tissues were associated with treatment outcomes, as determined by IMC. The gene signatures of IL7R low CD8 + T cell subsets correlated with type I IFN gene signature in the peripheral blood of paediatric and adult patients with lupus. IL7R low EM CD8 + T cells induced neutrophil extracellular trap (NET), a key inflammatory pathway in lupus pathogenesis, dependently of TNF-α and IFN-γ. Interpretation Our study provides insights into lupus pathogenesis by demonstrating the clinical and biological implications of cytotoxic and inflammatory IL7R low EM CD8 + T cell accumulation in lupus. This raises the prospect of therapeutic targets aimed at such CD8 + T cells. Funding Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (RS-2023-00249,430) as well as by the National Institutes of Health (1R01AR082203 and 2RF1AG056728 to IK, 5T32AR007107 to LO and JPY) and the Rheumatology Research Foundation (to IK).

摘要： The authors regret the typographical error on the last line of the first paragraph on page 3. “All discrepancies involved ambiguities in the second field of the typing results (i.e., DQ 1*01:04 versus DQ 1*01:05).” should read “All discrepancies i...

关键词： AD-like rash   Janus kinase inhibitor   psoriasis   upadacitinib   AD   atopic dermatitis   IL   interleukin   JAKi   Janus kinase inhibitor   PsA   psoriatic arthritis   TARC   Thymus and Activation-Regulated Chemokine   Th   T-helper  

摘要： Introduction Psoriasis is an immune-mediated disorder manifesting in the skin, joints, or both. Biologic treatments are an effective therapeutic option, producing long-term remission of psoriasis with a high safety profile. However, they are occas...

关键词： 人附睾蛋白4   单克隆抗体   蛋白纯化   杂交瘤细胞   侧向免疫层析  

摘要： 目的：制备抗人附睾蛋白4(human epididymis protein 4,HE4)单克隆抗体，并将其应用于侧向免疫层析（lateral flow immunoassay,LFIA）试剂盒的研制。方法：利用HE4重组蛋白作为免疫原进行动物免疫，采用杂交瘤技术筛选HE4融合细胞株，并通过动物体内诱生法大量制备抗人HE4单克隆抗体，并对抗体的亚型、亲和力、特异性等进行评价。将制备出的抗体应用于胶体金LFIA试剂盒，通过检测灵敏度、特异性等指标评价其应用价值。结果：成功筛选了3株杂交瘤细胞（3F7、3E5、5F10）并制备出抗人HE4单克隆抗体，与HE4的亲和力依次为252 pM、89 pM、104 pM；抗体与CA125、AFP、CEA、CYFRA21-1、CA72-4、BSA、HCG均没有交叉反应。3F7和3E5抗体的亚型是IgG2b,5F10抗体的亚型IgG1型。成功应用至LFIA试剂盒的检测限为100 pmol/L，特异性良好。结论：以人HE4重组蛋白为免疫原制备出三种具有高亲和力和良好特异性的抗人HE4单克隆抗体，并成功建立了胶体金LFIA试剂盒用于人血清HE4检测，为卵巢癌早期快速检测奠定基础。

关键词： 单克隆免疫球蛋白沉积病   肾损伤   临床病理特征   预后  

摘要： 目的分析累及肾脏的单克隆免疫球蛋白病(MG)的临床病理特征及肾脏预后。方法收集2018年1月至2022年12月在武汉大学人民医院经肾活检确诊的49例累及肾脏的单克隆免疫球蛋白病病人临床病理资料及预后资料。按照临床及病理结果分为免疫球蛋白相关淀粉样变性组及非淀粉样变性组,对比分析免疫球蛋白相关淀粉样变性病人的临床特征及肾脏预后。结果49例累及肾脏的单克隆免疫球蛋白病病人的发病年龄为(62.2±7.6)岁,大多数是男性(37例,75.5%),主要表现为蛋白尿、血尿及双下肢水肿。高脂血症、高血压病、糖尿病、心血管病及低蛋白血症病人分别占总人群的83.7%,34.7%,14.3%,34.7%及79.6%。肾脏病理类型有免疫球蛋白相关淀粉样变性(35例,57.1%)、管型肾病(6例,12.2%)、单克隆免疫球蛋白沉积病(6例,12.2%)及单克隆免疫球蛋白相关C3肾小球肾炎(2例,4.1%)。免疫球蛋白相关淀粉样变性病人轻链λ型(28例,80%)更常见,蛋白尿(P=0.193)更严重,高血压病(P=0.016)的比例更低。治疗后病人的肾脏预后较好(P=0.039)。结论累及肾脏的单克隆免疫球蛋白病病人多为老年男性,合并基础疾病,最常见的病理类型是免疫球蛋白相关淀粉样变性。治疗有助于改善累及肾脏的单克隆免疫球蛋白病病人肾脏预后。

关键词： T cell   cell therapy   immunophenotype   macrophage  

摘要： Macrophages and T cells communicate under homeostatic and pathological conditions. Previous studies elucidated biochemical crosstalk between macrophages and T cells. However, recent technological advances in multiplex tissue imaging reveal that these cells are often located proximally. Notably, recent clinical studies link the proximity of macrophages and T cells to cancer outcomes. These observations suggest that physical contact between the two cell types might influence their phenotype and activity. However, systematic investigations of the potential role of physical contact between these cells are lacking. To address this gap, we developed three-dimensional (3D) coculture assays to study the potential role of physical contact between naïve macrophages and activated CD8 T cells cultured in 3D Matrigel matrix. Under contact conditions, macrophages and T cells were coencapsulated in the same matrix, whereas under no-contact conditions, they were cultured in matrix, separated by a Transwell membrane. Our findings indicated that T cells changed their migration behavior by stopping and moving over the surface of naïve macrophages during coculture. We quantitatively determined T cells establish durable contact with macrophages, which informed our hypothesis that physical interactions between macrophage-T cells may induce phenotypic changes. Physical contact led to a 3-fold increase in IFN-γ secretion, a key effector molecule of CD8 T cells. The increase in IFN-γ was mediated by JAK and led to a 2-fold upregulation of ICAM-1 and increased PD-L1 expression. Our findings point to a model whereby activated T cells migrate toward macrophages and are held in proximity by ICAM-1 adhesion molecules, leading to increased production of IFN-γ and PD-L1 expression. These results establish that physical contact is an important determinant of macrophage and T cell states. Broadly, our study establishes a foundation to use biomaterials as a tool to provide mechanistic insights into h