Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 12, SE-413 45 Gothenburg, Sweden.
Thromb Haemost. 2013 Jan;109(1):112-7. doi: 10.1160/TH12-07-0468. Epub 2012 Nov 8.
Primary immune thrombocytopenia (ITP) is an autoimmune disease characterised by premature platelet destruction in spleen, liver and bone marrow and a diminished production of platelets. T-cells are important in all forms of autoimmunity including ITP; however, very little is known about T-cells in organs where platelets are destroyed. Our aim was to investigate differences in gene expression in peripheral blood-derived T-cells and bone marrow-derived T-cells between ITP patients and controls. T-cells and subsequent RNA were isolated from blood and bone marrow from chronic ITP patients and healthy controls followed by DNA microarray analysis. There were 1554 differentially expressed genes in peripheral blood-derived T-cells and 976 in bone marrow-derived T-cells between ITP patients and controls and three genes were verified with real-time PCR. Using Gene Ontology functional enrichment analysis we found that genes involved in growth, development, migration, chemotaxis, adhesion and apoptosis were enriched in bone marrow-derived T-cells in ITP. Immune-related genes involved in T-helper cell differentiation, T-cell chemotaxis, migration, immunoglobulin-mediated immune response and classical and alternative pathway complement activation were also enriched in bone marrow-derived T-cells in ITP. Only 213 T-cell genes were differentially expressed in both blood and bone marrow between ITP patients and controls. In conclusion, our findings show that genes involved in major pathophysiologic pathways in ITP such as T-helper cell differentiation, autoantibody response and complement activation are altered in bone marrow-derived T-cells in ITP patients compared with controls. This further supports the concept that bone marrow is an important compartment in ITP.
原发性免疫性血小板减少症 (ITP) 是一种自身免疫性疾病，其特征在于脾脏、肝脏和骨髓中血小板过早破坏以及血小板生成减少。T 细胞在包括 ITP 在内的所有自身免疫形式中都很重要；然而，对于在血小板被破坏的器官中 T 细胞知之甚少。我们的目的是研究 ITP 患者和对照者外周血衍生 T 细胞和骨髓衍生 T 细胞之间基因表达的差异。从慢性 ITP 患者和健康对照者的血液和骨髓中分离 T 细胞和随后的 RNA，然后进行 DNA 微阵列分析。ITP 患者和对照组之间的外周血衍生 T 细胞中有 1554 个差异表达基因，骨髓衍生 T 细胞中有 976 个差异表达基因，用实时 PCR 验证了三个基因。使用基因本体论功能富集分析，我们发现 ITP 中骨髓衍生 T 细胞中参与生长、发育、迁移、趋化、黏附和凋亡的基因富集。ITP 中骨髓衍生 T 细胞中还富集了与 T 辅助细胞分化、T 细胞趋化、迁移、免疫球蛋白介导的免疫反应以及经典和替代途径补体激活相关的免疫相关基因。仅在 ITP 患者和对照组之间的血液和骨髓中发现 213 个 T 细胞基因存在差异表达。总之，我们的研究结果表明，与对照组相比，ITP 患者骨髓衍生 T 细胞中与 T 辅助细胞分化、自身抗体反应和补体激活等 ITP 主要病理生理途径相关的基因发生改变。这进一步支持了骨髓是 ITP 重要部位的概念。
