【作者】 陈鹄；

【导师】 肖建华；

【作者基本信息】 南华大学 ， 免疫学， 2008， 硕士

【摘要】 目的:探讨HBV、CMV感染与ITP的关系,HBV、CMV感染所致ITP的发生机制,及其对ITP患者治疗与疗效的影响,总结HBV、CMV感染的ITP患者与阴性对照组ITP患者临床症状、体症、实验室检查及治疗方面的异同点,为预防、诊断及治疗HBV、CMV感染的ITP提供理论依据。方法:本文调查2006年1月-2008年7月在我院诊断为ITP并住院治疗的153例患者。153例在治疗前均行HBV血清标志物HBsAg、HBsAb、HBcAb、HBeAg、HBeAb检测,HBsAg阳性者为ITP患者感染了HBV;同时行外周血白细胞CMV PP65抗原检测,PP65阳性者为ITP感染了CMV。共有36例ITP患者HBsAg为阳性,31例ITP患者PP65阳性。将36例HBsAg阳性的ITP患者列为HBV感染组,31例PP65阳性的ITP患者列为CMV感染组,随机抽取同期住院的HBsAg、PP65均为阴性的35例ITP患者列为阴性对照组,并随机抽取血小板正常的健康体检者102例列为正常对照组。采用统计学方法对四个组的一般资料与临床表现进行了统计与分析,采用免疫学与细胞形态学方法对四个组的病毒感染情况、免疫学指标及骨髓细胞形态学进行了检测,采用不同的治疗方案对不同的ITP患者进行了治疗,并观察比较疗效。计量资料采用均数±标准差表示,两组间及组内均数的差异采用t检验,或Wilcoxon秩和检验进行分析,定性资料采用频数(率)表示,组间差异采用X2检验或Fisher精确概率检验。结果:1.病毒感染情况:153例ITP患者HBV感染率23.5%,CMV感染率20.3%,血小板正常的健康体检者HBV感染率9.8%,CMV感染率0%。ITP组与正常对照组相比有显著差异(P<0.05)。2.年龄状况:HBV感染组平均年龄46.12±10.3,CMV感染组平均年龄20.03±11.7,阴性对照组平均年龄31.89±12.2,感染组与阴性对照组比较有显著差异(P<0.05)。3.性别状况:ITP多见于女性,约为男性的2倍,但两个感染组ITP与阴性对照组ITP在性别上无显著性差异(P>0.05)。4.临床症状:HBV、CMV感染组ITP更易发生皮肤出血,与阴性对照组比较有显著性差异(P<0.05)。鼻衄及齿龈出血方面比较无显著性差异(P>0.05)。至于脏器出血,因病例数较少,未行统计学比较。5、入院时血小板数:HBV、CMV感染组ITP入院时血小板数与阴性对照组相比无显著性差异(P>0.05)。6、免疫学指标:免疫学指标检测包括补体(C3、C4)、PAIgG及T淋巴细胞亚群的检测。HBV、CMV感染组ITP补体水平、PAIgG及T淋巴细胞亚群与阴性对照组ITP相比较无显著性差异(P>0.05)。但ITP与正常对照组相比这三项指标有显著性差异(P<0.05), ITP患者补体水平下降,PAIgG明显增高,T淋巴细胞亚群比例失调,CD4百分比减低,CD8百分比增高。7、骨髓细胞学检查:36例感染了HBV的ITP出现了2例骨髓有核细胞增生减低,1例脾功能亢进骨髓象,31例感染了CMV的ITP出现了1例骨髓有核细胞增生减低。对三组ITP骨髓巨核细胞分析比较,HBV、CMV感染组ITP骨髓巨核细胞均值都少于阴性对照组,二者之间有显著性差异(P<0.05),提示HBV、CMV感染组ITP骨髓巨核细胞代偿增生性反应不及阴性对照组,HBV、CMV感染组幼稚型巨核细胞比例高,颗粒型巨核细胞比例少,与阴性对照组相比有显著性差异(P<0.05),提示HBV、CMV感染的ITP骨髓巨核细胞成熟停滞阶段更早。8、治疗方案与治疗效果:三组ITP首先均按常规方案行糖皮质激素治疗,于治疗第三天与第7天检测血小板并进行分析,HBV、CMV感染组血小板上升慢,治疗总有效率低,与阴性对照组相比有显著性差异(P<0.05)。糖皮质激素治疗效果较差的20例伴CMV感染的ITP,用糖皮质激素治疗的同时伍用更昔洛韦,27例伴HBV感染的ITP,同时伍用IFN-α,可明显提高治疗效果,总有效率达85.0%和74.1%。结论:1、153例ITP患者HBV感染率23.5%,CMV感染率20.3%,102例血小板正常的健康体检者其HBV感染率9.8%,CMV感染率0%。ITP患者与正常健康体检者之间两种病毒感染率存在显著性差异(P<0.05),因此HBV、CMV感染可能是诱发ITP的病毒之一。2、HBV、CMV感染组ITP患者更易发生皮肤出血;HBV、CMV感染的ITP患者骨髓巨核细胞代偿增生性反应不及阴性对照组,且巨核细胞成熟停滞阶段更早,少数可导致骨髓抑制。3、ITP组补体水平下降,PAIgG明显增高,外周血CD4百分比减低,CD8百分比增高,提示了ITP患者不仅有体液免疫紊乱,同时存在细胞免疫异常。4、感染了HBV、CMV的ITP患者单纯用糖皮质激素治疗疗效较差,CMV感染的ITP患者若伍用更昔洛韦,HBV感染的ITP患者若伍用IFN-α,可缩短病程,提高治疗效果。更多还原

【Abstract】 Objective:To study the relationship between the ITP and infection of HBV and CMV, and the cause of the ITP disease and curative effect of ITP patients with HBV or CMV infection ; to summarize the similarities and differences of clinic symptom,sign,laboratory experiments and treatments , and provide theoretical basis for prevention .diagnosis and treatment of the ITP disease with HBV and CMV infection .Methods:153 cases of ITP in-patients in our hospital (from January 2006 to July 2008 ) were studied. All patients were measured with serum remarks of HBV such as HBsAg ,HBsAb,HBcAb,HBeAg, HBeAb and the antigens of CMV pp65 of white blood cell in periperal vein .The positive results of HBsAg and pp65 determined that the ITP patients were infected by HBV and CMV respectively. 36 cases of HBsAg positive reaction and 31 cases of pp65 positive reaction in ITP patients were divided into HBV and CMV groups individualy. 35 ITP patients with negative reaction in both HBsAg and pp65 and 102 cases of health people with normal platelet count were randomly divided into negative group and normal control group individualy. The general clinical data of manifestation, laboratory test and therapy were analyzed with statistics method. Measuring data were indicated with±S , counting date were incated with frenquency . All results were analyzed with T test , analysis of variance ,chi-square test . Wilcoxon test and Fisher test .Results:1. Virus infective rates:the infective rates of HBV and CMV in ITP patients were 23.5% and 20.3% respectively , but those who in normal control with normal platelet count were 9.8% and 0% respectively . These were significantly difference between in infective group and normal control ( p<0.05 ) . 2 . Age: the average age of ITP patients with HBV or CMV infection and negative controls were 46.12+10.3 . 20.03+11.7 and 31.89+12.2 years, age variance between infective and negative group had significantly difference. 3. Sexual distinction :there were not significantly difference in ITP patients with HBV or CMV infection and negative group (P>0.05 ) . 4. Clinical manifestation: ITP patients with HBV or CMV infection were inclined to suffer from skin hemorrhage in comparison with negative group ( P<0.05) .Organ hemorrhage were not taken into account for insufficient cases . 5. Platelet count of the patients being hospitalized : the significantly deference between the ITP group with HBV or CMV infection and negation group(P>0.05) was not found. 6. Immunobiology indexes: immunobiology examinations included complement ( C3 . C4 ) , PAlgG and subgroup of T lymphocyte . These were not notable variance in ITP patients with negative or positive HBV and CMV infection in complement level、PAlgG and T lymphcyte subgroup (P>0.05 ) . By comparison with between ITP patients group and the normal group, the results showed significantly deference ( P<0.05 ), the ITP patients were lower level of complement, low proportoin of the CD4 T cells, and higher level of PAlgG and high proportion of CD8 T cells , and the T lymphocyte subgroup was disorder. 7.Bone marrow cytomorphologic examination:In the 36 ITP patients that have been infected HBV, there are two patients that bone marrow karyocyte proliferation have decreased. and there are one patient that hypersplenism. In the 31 ITP patients that have been infected CMV, there are one patient that bone marrow karyocyte proliferation have decreased. To analysis the two groups, the average of marrow megacaryocyte numbers are lower than negative control, there was a significance difference (P<0.05).Indicate that HBV or CMV infected groups of ITP patients are compensation of marrow productive reaction is inferior to negative control. The ration of infantilism megacaryocyte from the HBV or CMV infected groups is higher, and the granular megakaryocyte is lower, The difference is notable which compared with the negative control (P<0.05). Indicate that bone megakaryocytic from the ITP patients who infected HBV or CMV maturation lag more earlier.8.Treatment menthod and effect:after 3 days and 7 days with glucocorticoids therapy , HBV and CMV group showed slow- ascending platelet count and low treatmental curative effect in comparison with negative group (P<0.05 ) . The total efficiency of combined therapy,which glucocorticoids and ganciclovir in 20 ITP patients with CMV infection and gucocorticoids and IFN-αin 27 ITP patients with HBV infection, were 85.0% and 74.1% respectively .Conclusions:1. The infective rates of HBV and CMV in ITP patients were higher than those of normal control, HBV and CMV may be one of the viruses of the cause ITP disease. 2. The average age span had significantly deference in the negative group and HBV and CMV infection group. 3. Those ITP patients with HBV or CMV infection were inclined to occur skin hemorrhage. The ITP showed low level of platelet count, complement, the low proportion of CD4 T and higher level of PAlgG, high proportion of CD8 T, and the proportion of T lymphocyte subgroup was disorder, these results indicated both cellular and humoral immunity play important role in ITP . 4. The method of the combined therapy those ITP patients with HBV or CMV infection was efficient, glucocorticoids and ganciclovir was used in the patients of ITP with CMV infection and gucocorticoids and IFN-αwas used in ITP patients with HBV infection.更多还原