固有免疫细胞对ITP骨髓巨核细胞和血小板的破坏作用  

Destruction of ITP bone marrow megakaryocytes and platelets by innate immune cells

作　　者：胡金莲 张琳琳 李卓瓦 韩冰 吴强强 崔为同 梁亚俊 孙黎飞 HU Jinlian;ZHANG Linlin;LI Zhuowa;HAN Bing;WU Qiangqiang;CUI Weitong;LIANG Yajun;SUN Lifei(Key Laboratory of Qilu Medical University,Zibo 255300,China;Hematological Oncology Laboratory,Zibo 148 Hospital,Zibo 255300,China;Ji'nan Nursing Vocational College,Ji'nan 250100,China)

机构地区：[1]齐鲁医药学院重点实验室,淄博255300 [2]淄博148医院血液肿瘤实验室,255300 [3]济南护理职业学院,250100

出　　处：《免疫学杂志》2022年第12期1080-1084,共5页Immunological Journal

基　　金：山东省自然科学基金项目(ZR2019PC053);齐鲁医药学院校级基金课题(XJ19ZK01-03)。

摘　　要：目的 探讨EBV、HSV-Ⅰ/Ⅱ、CMV及MP感染早期,固有免疫细胞对原发免疫性血小板减少症(ITP)骨髓巨核细胞和血小板的破坏特征及临床意义。方法 化学发光免疫法检测患者血清EB病毒(EBV)、单纯疱疹病毒Ⅰ/Ⅱ型(HSV-Ⅰ/Ⅱ)、巨细胞病毒(CMV)、肺炎支原体(MP)等IgM和IgG抗体,ELISA法检测血小板抗体(PA-Ig),流式细胞术(FACS)检测外周血淋巴细胞比例。瑞氏染色观察骨髓中巨核细胞和血小板的破坏状态,免疫荧光染色(IF)观察MΦ表面FcγRⅠ和巨核细胞膜表面抗人IgG表达状态,细胞免疫和细胞化学染色,观察免疫细胞HLA-DR表达和过氧化物酶(POX)释放。结果 76例ITP患者中有43例分别伴有血清EBV、HSV-Ⅰ/Ⅱ和CMV特异性IgM抗体升高,IgG抗体正常。30例伴有MP特异性IgM升高,IgG正常。另3例血清HSV-Ⅰ/Ⅱ和MP特异性IgM均升高,IgG水平降低。MP感染者PA-IgM升高为(60.30±20.40) pg/L(P<0.05),其他PA-Ig均为正常。患者外周血CD3~+CD4~+Th细胞比例均显著升高为52.16%±3.21%(P<0.05)。骨髓巨噬细胞(MΦ)胞质中吞噬大量血小板。这些MΦ表面有少量FcγRⅠ灶性表达,巨核细胞膜表面抗人体IgG IF阴性。该类ITP患者骨髓中MΦ、树突状细胞(DC)和巨核细胞均高表达HLA-DR,活化的中性粒细胞释放大量POX。针对性抗感染联合短疗程小剂量糖皮质激素,能抑制对血小板的破坏。重症患者联合IVIg冲击能提高疗效。结论 EBV、HSV-Ⅰ/Ⅱ、CMV及MP感染早期,以Mφ和中性粒细胞为代表的固有免疫细胞对骨髓中病变的巨核细胞和血小板的破坏作用是此类ITP骨髓病理损伤特点;及时有效的抗感染联合小剂量糖皮质激素治疗对控制病情进展至关重要。This study was designed to investigate the characteristics and clinical significance of innate immune cells-induced destruction of megakaryocytes and platelets in the bone marrow of primary immune thrombocytopenia(ITP) patients in the early stage of EBV, HSV-Ⅰ/Ⅱ, CMV and MP infection. IgM and IgG antibodies against Epstein-Barr virus(EBV), herpes simplex virus type Ⅰ/Ⅱ(HSV-Ⅰ/Ⅱ), cytomegalovirus(CMV) and Mycoplasma pneumoniae(MP) were detected by chemiluminescence immunoassay. Platelet antibodies(PA-Ig) were detected by ELISA;flow cytometry(FACS) was used to detect the proportion of peripheral blood lymphocytes;the destruction of megakaryocytes and platelets in bone marrow was observed by Wright’s staining. The expression of FcγRⅠ on macrophages(Mφ) membrane surface and theexpression of anti-human IgG on megakaryocytemembrane surface were observed by immunofluorescencestaining(IF);the expression of HLA-DR and the releaseof peroxidase(POX) from immune cells were observed bycellular immunocytochemical staining. Among the 76 ITPcases, 43 cases showed elevated levels of serum EBV,HSV-Ⅰ/Ⅱ and CMV specific IgM antibodies, and normal level of IgG antibodies;30 patients showed increased MP-specific IgM level and normal IgG level. For the other 3 cases, HSV-Ⅰ/Ⅱ and MP-specific IgM levels were increased,while IgG levels were decreased. The level of PA-IgM in MP-infected patients raised to(60.30±20.40) pg/L(P<0.05), while other PA-Ig levels were normal. Furthermore, the proportion of CD3CD4Th cells in peripheral blood ofpatients was significantly increased to 52.16%±3.21%(P<0.05). There were some Mφ that phagocytosed a largenumber of platelets in the bone marrow. A small amount of foci expression of FcγRⅠ was observed on the surface ofthese Mφ, and anti-human IgG IF was negative on the surface of megakaryocytes. HLA-DR was highly expressed inMφ, dendritic cells(DC) and megakaryocytes of these ITP patients, and the activated neutrophils released a largeamount of POX. In conclusion, in the ear

关 键 词：感染免疫 固有免疫 原发免疫性血小板减少症 分型诊断 

分 类 号：R392.6[医药卫生—免疫学]