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T 细胞上失调的 CD38 表达与抗黑色素瘤分化相关基因 5 阳性皮肌炎中的快速进展性间质性肺病有关。

Dysregulated CD38 expression on T cells was associated with rapidly progressive interstitial lung disease in anti-melanoma differentiation-associated gene 5 positive dermatomyositis.

机构信息

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.

Sichuan Clinical Research Center for Laboratory Medicine, Chengdu, China.

出版信息

Front Immunol. 2024 Nov 11;15:1455944. doi: 10.3389/fimmu.2024.1455944. eCollection 2024.

Abstract

BACKGROUND

Anti-melanoma differentiation-associated gene 5 positive dermatomyositis (MDA5+ DM) is a life-threatening disease due to rapidly progressive interstitial lung disease (RP-ILD). We aimed to investigate the expression profile of T cell subsets in MDA5+ DM patients, seeking for possible disease-causing T cell subsets and potential biomarkers to distinguish ILD, especially RP-ILD patients.

METHODS

Peripheral blood T cell subpopulations were immunophenotyped in 24 MDA5+ DM patients and 21 healthy controls (HCs) by flow cytometry. The proportion of T cell subsets and clinical characteristics were analyzed. The quantitative determination of cytokines in the plasma was measured by using a microsphere-based immunofluorescence assaying kit.

RESULTS

The proportion of naïve and CD38+ T cells were much higher, whereas the proportion of central memory T cells were lower in MDA5+ DM patients than in HCs. Notably, the proportion of CD38+CD4+ T cells and CD38+CD8+ T cells on T cells in in RP-ILD group were significantly elevated compared to C-ILD, non-ILD group and HCs. Moreover, serum IFN-α levels were significantly increased in MDA5+ DM patients with RP-ILD. Further, the frequencies of CD38+CD4+ T cells and CD38+CD8+ T cells were positively correlated with IFN-α levels. Finally, ROC analysis indicated that CD38+CD4+ T cells and CD38+CD8+ T cells could be potential biomarkers for predicting ILD/RP-ILD in MDA5+ DM patients.

CONCLUSION

Dysregulated CD38 expression on T cell subsets was associated with lung involvement, especially RP-ILD in MDA5+ DM patients. CD38+ T cell subsets could be used as potential biomarkers for predicting ILD/RP-ILD in MDA5+ DM patients.

摘要

背景

抗黑色素瘤分化相关基因 5 阳性皮肌炎(MDA5+DM)由于快速进展性间质性肺病(RP-ILD),是一种危及生命的疾病。我们旨在研究 MDA5+DM 患者 T 细胞亚群的表达谱,寻找可能导致疾病的 T 细胞亚群和潜在的生物标志物来区分ILD,特别是 RP-ILD 患者。

方法

通过流式细胞术对 24 例 MDA5+DM 患者和 21 例健康对照者(HCs)的外周血 T 细胞亚群进行免疫表型分析。分析 T 细胞亚群的比例和临床特征。使用基于微球的免疫荧光分析试剂盒测定血浆中细胞因子的定量。

结果

与 HCs 相比,MDA5+DM 患者的幼稚和 CD38+T 细胞比例明显更高,而中央记忆 T 细胞比例更低。值得注意的是,在 RP-ILD 组中,T 细胞上的 CD38+CD4+T 细胞和 CD38+CD8+T 细胞的比例明显高于 C-ILD、非-ILD 组和 HCs。此外,MDA5+DM 患者中具有 RP-ILD 的 IFN-α 水平显著升高。此外,CD38+CD4+T 细胞和 CD38+CD8+T 细胞的频率与 IFN-α 水平呈正相关。最后,ROC 分析表明,CD38+CD4+T 细胞和 CD38+CD8+T 细胞可能是预测 MDA5+DM 患者 ILD/RP-ILD 的潜在生物标志物。

结论

T 细胞亚群上 CD38 的表达失调与肺部受累有关,特别是 MDA5+DM 患者的 RP-ILD。CD38+T 细胞亚群可作为预测 MDA5+DM 患者 ILD/RP-ILD 的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a09c/11586385/ba1c04ae529a/fimmu-15-1455944-g001.jpg

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