Peninsula Medical School, University of Exeter and Royal Devon and Exeter Hospital, Exeter, UK.
J Clin Immunol. 2010 Sep;30(5):649-58. doi: 10.1007/s10875-010-9429-y. Epub 2010 Jun 9.
Systemic lupus erythematosus (SLE) and rheumatoid arthritis have complex genetic traits, but in both autoimmune diseases, dysfunctional apoptosis appears to play a part in disease pathology. This study examined the levels of in vitro apoptosis in lymphocytes from healthy, rheumatoid arthritis (RA) and SLE individuals and related observed differences to their lymphocyte apoptosis gene profiles.
Lymphocytes were assessed for cell death by nuclear pyknosis and DNA fragmentation. Control, SLE and RA apoptosis gene profiles were obtained by quantitative real-time polymerase chain reaction (QRT-PCR) analysis.
The mean levels of pyknosis in RA and SLE freshly isolated lymphocytes were significantly higher than in control lymphocytes. Ninety-three apoptosis genes were analysed by QRT-PCR of mRNA from RA, SLE and healthy lymphocytes. We identified significant differences (p < 0.05) in the expression of the same 11 of 93 and two of 93 apoptotic genes in individual SLE and RA patients tested as compared with controls.
We propose that similarly altered expression of specific apoptotic regulatory genes (e.g., the death effector domain-containing DNA-binding protein and apoptosis-associated speck-like protein containing a CARD) occurs in the lymphocytes of individual patients with SLE or RA that may influence the extent and rate of spontaneous apoptosis in these autoimmune conditions.
系统性红斑狼疮(SLE)和类风湿关节炎(RA)具有复杂的遗传特征,但在这两种自身免疫性疾病中,凋亡功能障碍似乎都与疾病的病理有关。本研究检测了健康者、RA 和 SLE 个体淋巴细胞的体外凋亡水平,并将观察到的差异与他们的淋巴细胞凋亡基因谱相关联。
通过核固缩和 DNA 片段化检测淋巴细胞的细胞死亡。通过实时定量聚合酶链反应(QRT-PCR)分析获得对照、SLE 和 RA 的凋亡基因谱。
RA 和 SLE 新鲜分离的淋巴细胞的核固缩平均水平明显高于对照组淋巴细胞。对 RA、SLE 和健康淋巴细胞的 mRNA 进行了 93 个凋亡基因的 QRT-PCR 分析。与对照组相比,我们在个体 SLE 和 RA 患者中检测到相同的 11 个和两个凋亡基因的表达存在显著差异(p<0.05)。
我们提出,SLE 或 RA 个体淋巴细胞中特定凋亡调节基因(例如,死亡效应结构域包含 DNA 结合蛋白和凋亡相关斑点样蛋白含有 CARD)的表达同样发生改变,这可能影响这些自身免疫性疾病中自发凋亡的程度和速度。