Hematologic Disease Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Xinjiang Uygur Autonomous Region Research Institute of Hematology, Urumqi, China.
Acta Haematol. 2023;146(4):267-276. doi: 10.1159/000529963. Epub 2023 Mar 14.
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia. Herein, we sought to identify potential immune-related therapeutic targets in ITP.
The differentially expressed genes (DEGs) between ITP patients and controls in GSE43177 and PRJNA299534 were analyzed. The intersections of the two DEG groups were screened as common genes, and enrichment analysis was performed. Additionally, differential analysis of immune cell levels between ITP and controls was performed. Changes in the proportions of T follicular helper (Tfh) and follicular regulatory T (Tfr) cells in peripheral blood samples from ITP patients, ITP patients responding to therapy, and healthy controls were identified. The expression changes in B-cell lymphoma (Bcl)-6 and interleukin (IL)-21 were further evaluated.
A total of 76 common genes were identified, and enrichment analysis found that these genes were mainly associated with neutrophil-mediated immunity, the MAPK signaling pathway, and the FOXO signaling pathway. Furthermore, we found different levels of Tfh cells in patients with ITP and controls. The level of Tfh cells in the peripheral blood is significantly increased in ITP patients and declines after responding to therapy. The Tfr/Tfh ratio was reduced in ITP patients and increased after responding to therapy. IL-21 and Bcl-6 were more highly expressed in ITP patients than in controls.
We identified abnormally expressed genes in ITP related to immune-related biological functions. We further identified the changes in Tfh and Tfr cells during ITP treatment. This provides a rationale for immunotherapy in ITP patients.
免疫性血小板减少症(ITP)是一种以血小板减少为特征的自身免疫性疾病。在此,我们试图确定 ITP 中的潜在免疫相关治疗靶点。
分析 GSE43177 和 PRJNA299534 中 ITP 患者和对照之间差异表达的基因(DEGs)。筛选两组 DEG 的交集作为共同基因,并进行富集分析。此外,还对 ITP 与对照之间免疫细胞水平进行差异分析。鉴定 ITP 患者、对治疗有反应的 ITP 患者和健康对照者外周血样本中滤泡辅助 T(Tfh)和滤泡调节性 T(Tfr)细胞比例的变化。进一步评估 B 细胞淋巴瘤(Bcl)-6 和白细胞介素(IL)-21 的表达变化。
共鉴定出 76 个共同基因,富集分析发现这些基因主要与中性粒细胞介导的免疫、MAPK 信号通路和 FOXO 信号通路有关。此外,我们发现 ITP 患者和对照者之间 Tfh 细胞水平不同。ITP 患者外周血中 Tfh 细胞水平明显升高,治疗后下降。ITP 患者的 Tfr/Tfh 比值降低,治疗后升高。IL-21 和 Bcl-6 在 ITP 患者中的表达高于对照者。
我们鉴定出与免疫相关生物学功能相关的 ITP 中异常表达的基因。我们进一步鉴定了 ITP 治疗过程中 Tfh 和 Tfr 细胞的变化。这为 ITP 患者的免疫治疗提供了依据。