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探讨胰岛素样生长因子结合蛋白-1在识别特发性多中心 Castleman 病类型中的作用:对 mTOR 信号通路的影响。

Exploring the role of insulin-like growth factor binding protein-1 in identifying idiopathic multicentric Castleman's disease types: Implications for the mTOR signaling pathway.

机构信息

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Clincal Research Center, Nagasaki University Hospital, Nagasaki, Japan.

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

出版信息

Clin Immunol. 2023 Nov;256:109798. doi: 10.1016/j.clim.2023.109798. Epub 2023 Sep 30.

Abstract

OBJECTIVE

To determine the molecular differences between iMCD-thrombocytopenia, anasarca, fevers, reticulin myelofibrosis, organomegaly (TAFRO), and iMCD-not otherwise specified (NOS).

METHODS

CD4-positive T cells were isolated from two iMCD-TAFRO and two iMCD-NOS patients for RNA sequencing comparison. Serum proteins of two iMCD-TAFRO and four iMCD-NOS patients were comprehensively analyzed to identify pathogenesis-associated proteins. IGFBP-1 protein, extracted from serum analysis, was compared to healthy controls, iMCD, systemic lupus erythematosus, and rheumatoid arthritis patients.

RESULTS

RNA sequencing of CD4-positive T cells revealed enhanced mTOR-related signaling in iMCD-TAFRO compared to iMCD-NOS. Comprehensive serum analysis found IGFBP-1 linked to iMCD pathogenesis, significantly higher in iMCD-TAFRO. This protein may be elevated in patients with iMCD caused by an enhanced mTOR pathway.

CONCLUSION

The mTOR pathway is suggested to be activated in iMCD-TAFRO compared to iMCD-NOS, which may elevate the protein IGFBP-1. This protein may be a biomarker to distinguish iMCD-TAFRO from iMCD-NOS.

摘要

目的

确定 iMCD-血小板减少症、全身性水肿、发热、网状纤维骨髓纤维化、器官肿大(TAFRO)和 iMCD-未特指型(NOS)之间的分子差异。

方法

从两名 iMCD-TAFRO 和两名 iMCD-NOS 患者中分离 CD4阳性 T 细胞进行 RNA 测序比较。对两名 iMCD-TAFRO 和四名 iMCD-NOS 患者的血清蛋白进行全面分析,以鉴定与发病机制相关的蛋白。从血清分析中提取 IGFBP-1 蛋白,并与健康对照、iMCD、系统性红斑狼疮和类风湿关节炎患者进行比较。

结果

CD4阳性 T 细胞的 RNA 测序显示,与 iMCD-NOS 相比,iMCD-TAFRO 中 mTOR 相关信号增强。全面的血清分析发现 IGFBP-1 与 iMCD 发病机制相关,在 iMCD-TAFRO 中显著升高。这种蛋白可能在由 mTOR 途径增强引起的 iMCD 患者中升高。

结论

与 iMCD-NOS 相比,iMCD-TAFRO 中 mTOR 途径被激活,可能会升高 IGFBP-1 蛋白。这种蛋白可能是区分 iMCD-TAFRO 和 iMCD-NOS 的生物标志物。

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