【作者】 王云；

【导师】 冀学斌； 徐淼；

【作者基本信息】 山东大学 ， 内科学（血液病学）（专业学位）， 2024， 硕士

【摘要】 研究目的探究抗血小板膜糖蛋白抗体的种类对原发性免疫性血小板减少症(Primary immune thrombocytopenia,ITP)不同治疗反应的影响,旨在阐明抗血小板膜糖蛋白抗体对ITP患者个体治疗的指导意义。研究方法收集2016年1月至2023年7月于山东大学齐鲁医院住院治疗的459例ITP患者的资料进行回顾性分析,记录患者姓名、性别、年龄、治疗方案与血小板计数等临床资料,应用单克隆抗体特异性血小板抗原固定化术(MAIPA)检测患者抗血小板膜糖蛋白抗体的表达。采用SPSS 26.0软件进行统计分析。探究患者一般临床资料与抗体表达的相关性,比较不同的抗体类型对ITP患者治疗反应的影响。应用GraphPad Prism 5作图。P<0.05(双侧)表示有统计学意义。研究结果1.本研究纳入459名ITP患者,男性177例,女性282例,男女比例5:8,中位年龄31.0(51.0-62.0)岁,不同抗体组间的性别、年龄差异无统计学意义(P>0.05)。在未区分治疗方案的情况下,不同抗体种类之间,治疗总体反应无统计学差异(P=0.212)。2.分析性别和年龄是否影响ITP患者表达抗血小板膜糖蛋白抗体,结果示:男性患者抗体阳性率高于女性患者(24.29%vs21.98%,P<0.01)。小于40岁年龄组的抗体阳性率为18.01%(29人),40-60岁年龄组抗体阳性率31.03%(54人),大于60岁年龄组抗体阳性率为17.74%(22人),差异有统计学意义(P=0.005)。3.为了进一步探究抗血小板膜糖蛋白抗体的表达与性别、年龄的关系,进行Logistic回归分析。纳入年龄和性别等构建Logistic回归模型,结果示相对于男性,女性患者抗GPIb/IX抗体阳性率更低(OR=0.384,95%CI 0.17-0.85,P=0.019);年龄在40-60岁的ITP患者抗GPIIb/IIIa抗体及GPIb/IX抗体双阳性(OR=2.52,95%CI 1.03-6.20,P=0.044)或者抗GPIIb/IIIa抗体单阳性的可能性更大(OR=2.79,95%CI 1.07-7.26,P=0.035)。4.通过卡方检验分析ITP治疗反应与抗血小板膜糖蛋白抗体种类的关系,结果示抗GPIb/IX抗体和抗GPIIb/IIIa抗体的表达与糖皮质激素单药治疗、糖皮质激素联合人免疫球蛋白、利妥昔单抗和地西他滨等治疗的有效率无关(P>0.05)。血小板生成素受体激动剂(Thrombopoietin receptor agonists,TPO-RAs)或重组人血小板生成素(Recombinant human thrombopoietin,rhTPO)的疗效与抗 GPIb/IX 抗体相关(P<0.05)。5.纳入性别、年龄、血小板计数等构建多因素Logistic回归模型,结果发现,基线血小板计数越高,对TPO-RAs或rhTPO的治疗反应越不显著(OR=0.98,95%CI 0.96-1.00,P=0.041);性别、年龄不影响患者对治疗的反应。结论ITP治疗方法多样,不同人群对治疗的反应难以预测,且一些治疗方案成本较高,预测治疗反应对减轻患者经济负担具有重要意义。抗血小板自身抗体在其发病机制中占据重要地位,男性患者抗体阳性率高于女性,40-60岁年龄组患者抗体阳性率高于其他年龄组。男性患者检测抗血小板膜糖蛋白抗体或许对ITP的诊断具有更重要的意义。TPO-RAs或rhTPO的治疗反应与抗GPIb/IX抗体相关。抗血小板膜糖蛋白自身抗体可能成为预测TPO-RAs或rhTPO疗效的指标之一。更多还原

【Abstract】 ObjectiveExplore the effect of anti-platelet membrane glycoprotein antibody types on different therapeutic responses to idiopathic immune thrombocytopenia(ITP)in order to clarify the guiding significance of anti-platelet membrane glycoprotein antibody types in the treatment of patients with ITP.MethodsMedical data of 459 ITP cases hospitalized in Qilu Hospital of Shandong University from January 2016 to July 2023 were reviewed.Clinical data such as name,gender,age,treatment regimens and platelet count were recorded.The expression of anti-platelet membrane glycoprotein antibody was detected by monoclonal antibody immobilization of platelet antigen assay(MAIPA).SPSS 26.0 software was used for statistical analysis.To explore the correlation between patients’ general clinical data(such as gender and age)and antibody expression,and compare the effect of different antibody types on the treatment response of ITP patients.Use GraphPad Prism 5 to plot.P<0.05(bilateral)indicated statistical significance.Results1.459 ITP patients were included in this study,including 177 males and 282 females,with a male to female ratio of 5:8 and a median age of 31.0(51.0-62.0)years.There were no significant difference in gender and age among different antibody groups(P>0.05).There was no significant difference in overall response rate among different antibody types without distinguishing specific treatment regimens(P=0.212).2.To analyze whether gender and age affected the expression of anti-platelet membrane glycoprotein antibody types in ITP patients,the positive rate of antibodies in male patients was higher than that in female patients(24.29%vs 21.98%,P<0.01).The antibody positive rate was 18.01%(29 people)in the age group below 40 years old,31.03%(54 people)in the age group between 40 and 60 years old,and 17.74%(22 people)in the age group above 60 years old(P=0.005).3.In order to further explore whether the expression of anti-platelet membrane glycoprotein antibodies is related to gender and age,Logistic regression analysis was conducted.Multivariate logistic regression model was constructed including age and gender,and the results showed that the positive rate of anti-GPIb/IX antibody was lower in female patients than in male patients(OR=0.384,95%CI 0.17-0.85,P=0.019).ITP patients aged 40-60 years were more likely to be double-positive for anti-GPIIb/IIIa and GPIb/IX antibodies(OR=2.52,95%CI 1.03-6.20,P=0.044)or single-positive for anti-GPⅡb/Ⅲa antibodies(OR=2.79,95%CI 1.07-7.26,P=0.035).4.Chi-square test was used to analyze the therapeutic efficacy of ITP and the expression types of anti-platelet membrane glycoprotein antibodies,and the results showed that the expression of anti-GPIb/IX antibodies and anti-GPIIb/IIIa antibodies were not correlated with the remission rate of glucocorticoid monotherapy,glucocorticoid combined with intravenous immunoglobulin,rituximab and decitabine therapy(P>0.05).The therapeutic response of thrombopoietin receptor agonists(TPO-RAs)or recombinant human thrombopoietin(rhTPO)was correlated with anti-GPIb/IX antibodies and anti-GPⅡb/Ⅲa antibodies(P<0.05).5.Gender,age and platelet count were included in the multifactor logistic regression model.The results showed that the higher the baseline platelet count,the less significant the treatment response to TPO-RAs or rhTPO(OR=0.98,95%CI 0.96-1.00,P=0.041).Gender and age did not affect the treatment response of ITP patients.ConclusionsThere are various treatment regimens for ITP,the response of different populations to treatments is difficult to predict,and the cost of some treatments is high,so predicting treatment response is of great significance to reduce the economic burden of patients.Anti-platelet autoantibodies play an important role in the pathogenesis,and their expression is different between different genders and ages.The antibody positive rate of male patients is higher than that of female patients,and the antibody positive rate of 40-60 years old patients is higher than that of other age groups.Detection of anti-platelet membrane glycoprotein antibodies in male patients may be more important for the diagnosis of ITP.The therapeutic response of TPO-RAs or rhTPO is correlated with anti-GPIb/IX antibodies and anti-GPⅡb/Ⅲa antibodies.Anti-platelet membrane glycoprotein autoantibodies may be one of the indicators to predict the efficacy of TPO-RAs or rhTPO.更多还原