CD72在免疫性血小板减少症中的基因表达

【作者】 周虎；

【导师】 杨仁池；

【作者基本信息】 北京协和医学院 ， 内科学， 2011， 博士

【摘要】 目的：研究免疫性血小板减少症(ITP)患者信号素Sema4D和其免疫受体CD72的基因表达情况、血浆Sema4D.血浆Th细胞因子IL-2, IL-4, IL-6和INF-γ水平及二者的相关性,探讨其在ITP发病机制中的作用。方法：采用放射免疫法(RIA)测定血浆细胞因子IL-2,IL-4,IL-6.水平,ELISA检测血浆sSema4D和INF-γ水平,实时荧光定量PCR法(RQ-PCR)检测Sema4D.cD72.IL-4和INF-γmRNA表达水平。结果：共检测39例ITP患者和23名正常对照,血浆工L-2水平未治疗ITP组(1.435±0.617ng/mL)显著低于完全缓解组为(3.100±2.410ng/mL,P<0.01)和正常对照组(2.272±1.385ng/mL,P<0.05),在缓解组和对照组间无统计学差异(P>0.05)。血浆IL-4水平未治疗ITP组(0.856±0.183ng/mL)和完全缓解组为(0.898±0.218ng/mL)显著高于正常对照组(0.714±0.170ng/mL,P<0.01),在缓解组和未治疗组间无统计学差异(P>0.05).IFN-γ/JL-4(Thl/Th2)mRNA水平在活动期ITP患者(中位数1.957,0.181-9.292)和缓解期患者(中位数2.499,0.186-29.32)是明显高于对照组(中位数0.819,0.018-4.88,P(0.01,P=0.01)。在缓解期和活动期患者之间无统计学差异(P>0.05)。活动期ITP患者CD72 mRNA(中位数1.664,0.184-9.659)的表达水平与正常对照组(中位数3.251,0.289-19.15,P<0.05.有明显差异,与完全缓解期患者相比(中位数3.491,0.266-47.38,P<0.05也有显著差异,但是缓解期患者与正常对照组的CD72mRNA的表达水平无统计学差异。未治疗组患者CD72 mRNA表达水平与血浆IL-2水平(P=0.036)及Sema4DmRNA表达水平(p=0.024)呈正相关。结论：CD72在ITP发病中可能起着一种负性调节的作用,ITP患者存在Thl/Th2细胞的失衡,CD72与Sema4D与IL-2存在一定相关性。目的：为探讨老年ITP患者的临床特征,合并症,治疗反应以及预后情况,我们对在我院1980-2009年间就诊的大于60岁的患者的临床资料进行了回顾性分析。研究对象和方法：我们共回顾性分析了525例(325例女性,200例男性)患者,中位年龄66岁(60-91岁)。结果：在最初诊断时,461例(87.8%)患者有出血症状,62.5%的患者合并有其他疾病,其中合并高血压为112例(22.1%),冠心病77例(14.7%)。144例患者(27.4%)没有接受任何治疗,299例患者(57%)仅接受一线治疗。14例患者行脾切除术,仅占患者总数的2.7%。90例长期随访患者,中位随访时间51个月(12-128月),总的治疗反应率68.8%(CR+PR)。31.2%患者未到CR或R,但是血小板中位数随访时为48.5×109/L(5-95×109/L)。直接或间接因治疗ITP相关死亡率为8%。结论：在60-69岁年龄段女性发病多于男性,出血症状更多,由于药物治疗近期和远期反应率较好,在老年患者中较少实施脾切除。尽管老年ITP因血小板减少死亡率较高,但是和其他死亡原因并无显著性差异。由此可认为老年ITP仍旧为一种良性疾病。更多还原

【Abstract】 Objectives:To explore the role of CD72 in the pathogenesis of immune thrombocytopenia (ITP), we detected CD72, Sema4D, IL-4 and IFN-γmRNA expression and the levels of plasma Sema4D, IL-2, IL-4, IL-6 and INF-γin ITP patients(n=39) and controls (n=23).Methods:The levels of plasma IL-2, IL-4 and IL-6 were assayed by radioimmunoassay (RIA), The levels of plasma INF-γand sSema4D were analyzed by enzyme-linked immunosorbent assay(ELISA). Sema4D, CD72, IFN-γand IL-4MRNA expression by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR).Results:The expression of CD72 mRNA in ITP patients (n=23) with active disease was significantly lower than that in patients in remission (P<0.05) (n=16) and controls (P<0.05) (n=23). The IFN-γ/IL-4 mRNA (Th1/Th2) expression in ITP patients with active disease and in remission was significantly higher than that in controls (P<0.01, P<0.05). The level of plasma IL-2 in ITP patients with active disease was significantly lower than that in patients in remission (P<0.05) and controls (P<0.05). The levels of plasma IL-4 in ITP patients with active disease and in remission were significantly higher than that of controls (P<0.01). The CD72 mRNA expression level correlated with Sema4DmRNA expression in peripheral blood mononuclear cells and level of plasma IL-2 in active ITP patients (P=0.024 and P=0.036).Conclusions:Our findings suggest that CD72 plays a negative role and correlate with Sema4D mRNA expression in peripheral blood mononuclear cells and level of plasma IL-2 in the active ITP patients. In this retrospective study, we evaluated the clinical features and the effects of various treatment modalities on the clinical course in elderly patients (i. e., age≥60 yr) diagnosed with immune thrombocytopenia (ITP) at our center from 1980 to 2009. We retrospectively examined the medical records of 525 (325 females,200 males) ITP patients. The median age of the patients at presentation was 66 years (range:60-91yr). At initial diagnosis,461 (87.8%) patients had signs of bleeding, we find 62.5% patients had co-existing diseases, the most prevalent of which were hypertension (n=112,22.1%) and coronary heart disease (n=77,14.7%). One hundred-and-Forty-four patients (27.4%) received no treatment, and 299 (57%) received first line treatment only. Fourteen patients (2.7%) underwent splenectomy. Ninety patients who have follow-up≥12months, (median51months, range,12-128months) the total rate of response was 68.8%(CR+PR).31.2%patients had not achieved CR or R, but the median platelets was 48.5×109/L (range,5-95×109/L). The death rate from causes directly related to ITP or its treatment was 8.0%with at last follow up in 113patients. In conclusion, there are more female aged patients during 60-69 years old. The splenectomy was rarely performed in patients more than 60 years old because of a good reponse to therapy. Even though the mortality was higher attributed to ITP or complications, this incidence was not significantly different from other death cause (p>0.05). This retrospective review represents the largest collection of elderly patients with ITP in China in a single center.更多还原