免疫相关性血细胞减少患者骨髓造血细胞岛的免疫损伤研究

目的探讨免疫相关性血细胞减少(immuno-related hematocytopenia,IRH)患者骨髓"造血细胞岛"(hematopoietic islands,HI)对病变造血细胞破坏的免疫机制。方法 ELISA法检测患者血清IL-12和IL-17水平,观察其体内炎性因子的含量,免疫荧光(immunofluorescence,IF)染色,观察其骨髓HI中免疫细胞Fcγ受体Ⅱ(Fcγrecepter Ⅱ,FcγRⅡ)、甘露糖受体(mannose receptor,MR)、IL-12、IL-17A、IL-17RA和ICAM-1表达,分析HI的相关病理作用。结果 37例患者血清IL-12和IL-17的水平分别为(318.59±20.13)ng/L和(45.81±8.27)ng/L,显著高于对照组(94.05±3.26)ng/L和(20.03±1.14)ng/L];经治疗后均下降近正常,较治疗前差异显著,P<0.01。患者骨髓中HI主要为抗体依赖性细胞毒(antibody dependent cell cytotoxicity,ADCC)型、巨噬细胞型(Mφ)和抗原提呈(antigen presenting,AP)型3种,HI中的免疫细胞高表达FcγRⅡ、MR,呈分泌状表达IL-12、IL-17A、IL-17RA和ICAM-1,在上述免疫分子的介导下,发挥体液免疫和细胞免疫及炎性损伤作用,破坏病变的造血细胞。结论 IRH患者骨髓中不同造血细胞岛是活化的免疫细胞破坏病变血细胞的不同免疫形式,是造血细胞在骨髓中"原位破坏的"重要场所。

Hematopoietic island injury in patients with immuno-related hematocytopenia

This study aimed study the roles of hematopoietic islands(HI) in clearance of injured hematopoietic cells in the bone marrow of patients with immuno-related hematocytopenia(IRH).ELISA was performed to detect serum level of IL-12 and IL-17 in patients with HI.Immunofluorescence(IF) staining was used for measuring the expression levels of FcrⅡ receptor(FcrⅡR),mannose receptor(MR),ICAM-1,IL-12,IL-17A,IL-17RA and ICAM-1 on immunocytes.We found that serum IL-12 and IL-17 were elevated significantly in 37 HI patients compared with the control group (318.59±20.13) ng/L vs(94.05±3.26) ng/L for IL-12,(45.81±8.27) ng/L vs(20.03±1.14) ng/L for IL-17].After immunosuppressive therapy,IL-12 and IL-17 levels decreased to normal levels which were lower than that of pretherapy obviously(P < 0.01).HI in IRH patients could mainly classified into three different types: antibody dependent cell cytotoxicity(ADCC) type,macrophages(Mф) type,and antigen presenting(AP) type.Immune cells in HI could highly express FcγRⅡ and MR,and also could secrete IL-12,IL-17A,IL-17RA and ICAM-1,which would help to destroy injured hematopoietic cells.In conclusion,different types of HI in bone marrow of IRH patients might be different immunological responses of those activated immunocytes to destroy target cells,and these different HI also might be important workshop for ’hemolysis in situ’ of hematopoietic cells in bone marrow.