骨髓造血细胞岛在免疫相关性血细胞减少患者中的异质性研究

The heterogeneity of hematopoietic islands in immuno-related hematocytopenia

目的:观察免疫相关性血细胞减少或免疫相关性全血细胞减少(Immuno-related hematocytopenia/immuno-relat-ed pancytopenia,IRH/IRP)患者骨髓"造血细胞岛"(Hematopoietic islands,HI)的不同性质,分析其与MHCⅠ/Ⅱ类分子和骨髓造血细胞抗人球蛋白(IgG)的关联,探讨相关免疫机制及其对临床诊疗的指导意义。方法:①对37例IRH/IRP患者骨髓涂片行常规瑞氏染色,观察HI的细胞成分和岛中免疫细胞性质;②细胞化学染色观察HI中免疫细胞过氧化物酶(POX)活性和铁贮存情况;③HLA-DR抗体免疫化学染色,观察免疫细胞MHCⅡ分子表达情况;④抗人IgG免疫荧光抗体(Immunofluores-cence,IF)染色,观察造血细胞和免疫细胞表面抗人IgG抗体表达;⑤观察不同HI在患者骨髓中出现的情况。结果:①HI中的造血细胞和免疫细胞各异,并与患者血沉和IgG、血清HLA-B27抗体浓度和过氧化物酶(POX)、HLA-DR和IF染色表达情况密切相关。②根据免疫细胞的生物学性质分为抗体依赖细胞介导的细胞毒作用(Antibody dependent cell cytotoxicity,AD-CC)型HI、巨噬细胞(Mφ)型HI、抗原提呈(Antigen presenting,AP)型HI、浆细胞型HI和幼粒细胞型HI 5种。③HI中幼稚的造血细胞膜上均表达抗人IgG荧光抗体,HI中免疫细胞与造血细胞接触处和抗原提呈细胞(Antigen presenting cells,APC)浆中呈现不同的强阳性IF颗粒。④Mφ型HI数量最多,常与ADCC型HI在血沉升高患者骨髓中同时出现,HLA-B27和血沉均升高的IRP患者骨髓中可同时存在ADCC型、Mφ型和AP型HI。结论:IRH/IRP患者骨髓幼稚造血细胞膜表面抗原改变产生抗人IgG抗体是HI产生的基础;HI异质性及在骨髓中出现的不同形式则为患者体液免疫和细胞免疫不同程度的活化对造血细胞多重性损伤的生物学表现。

Objective：To study the different characteristics of hematopoietic islands（HI）in immuno-related hematocytopenia（IRH）/ immuno-related pancytopenia（IRP）,study the relationship between it and MHC molecules and antihuman globulin of myeloid element（IgG）,investigate the relevant immune mechanisms and the guiding significance for clinical diagnosis and treatment.Methods： ①Wright＇s Staining was utilized for observing the immunocyte quantity and hematopoietic cell component in myeloid element islands of 37 patients with IRH/IRP;②Cytochemical staining was utilized for observing the peroxidase（POX） activity and the condition of iron storage of immune cells in HI;③Immunochemistry staining was utilized for observing the MHC Ⅱ（HLA-DR antigen）of antigen presenting cell in the bone marrow;④Immunofluorescence（IF） staining was utilized for observing anti-human IgG antibody in hematopoietic cells and immune cells;⑤Observing different types of HI in the bone marrow.Results：①The hematopoietic cells and immune cells were various in HI,and were closely related with ESR,IgG,serum HLA-B27,peroxidase（POX）,HLA-DR and IF.②According to the biological properties of immune cells,the HI were divided into five types：antibody dependent cell cytotoxicity（ADCC） type,macrophages（Mφ） type,antigen presenting type,plasma cells type and promyelocytic type.③Antihuman IgG fluorescent antibodies were expressed in all naive hematopoietic cell membranes of HI,and different strong positive IF particles were present in the contact position between immune cells and hematopoietic cells and the cytoplasms of antigen presenting cells（APC）;④Mφ-type HI was the most in number,and was often coexisted with ADCC-type HI in patients with higher erythrocyte sedimentation rate（ESR）.In the bone marrow of patients with both HLA-B27 and ESR increase,ADCC-type HI,Mφ-type HI and AP-type HI could been seen at the same time.Conclusions：The basis of HI is that the change of immature hematopoietic cell surface of patients with IRH/IRP results in antihuman IgG antibodies generation.The heterogeneity of HI is because humoral and cellular immune activation in different forms.