贫血患者调节性T细胞与人类白细胞抗原Ⅱ表达对血红蛋白影响分析

Effects of regulatory T cell and human leukocyte antigen classⅡmolecule expression in anaemia patients on haemoglobin

目的:人类白细胞抗原Ⅱ(HLA-Ⅱ)由抗原提呈细胞表达直接参与T细胞活化,调节性T细胞(Treg)在免疫系统中发挥调节免疫反应的重要作用。贫血是血液病学常见的疾病,病因众多。本文探讨不同贫血患者与HLA-Ⅱ分子表达及Treg细胞比例之间的相关性。方法:以自身免疫性溶血性贫血(AIHA)、骨髓衰竭性疾病(BMFS)、B细胞-浆细胞肿瘤侵犯骨髓、继发于感染或肝肾疾病的慢性病贫血患者为研究对象,检测以上疾病患者HLA-Ⅱ分子表达强度、Treg细胞比例及与贫血程度的相关性。结果:所有贫血患者的HLA-Ⅱ类分子表达在淋巴细胞和单核细胞中差异无统计学意义;AIHA患者血红蛋白含量与外周血Treg细胞比例呈负相关;BMFS患者Treg细胞比例与淋巴细胞HLA-Ⅱ表达呈正相关;B细胞-浆细胞肿瘤侵犯骨髓患者血红蛋白含量与淋巴细胞HLA-Ⅱ及HLA-DR表达呈正相关;继发于感染或肝肾疾病的慢性病贫血患者血红蛋白含量与单核细胞HLA-Ⅱ及HLA-DR表达呈负相关,外周血Treg细胞比例与淋巴细胞HLA-Ⅱ及HLA-DR表达呈正相关。结论:AIHA、BMFS、B细胞-浆细胞肿瘤侵犯骨髓、继发于感染或肝肾疾病的慢性病贫血患者的单核细胞免疫反应较健康供者活跃;B细胞-浆细胞肿瘤累及骨髓患者的恶性淋巴细胞通过低表达HLA分子来实现免疫逃逸及大量增殖;继发于感染或肝肾疾病的慢性病贫血促进单核细胞的活化,其Treg细胞比例与淋巴细胞HLA-Ⅱ分子表达相关;Treg细胞减少参与AIHA的发生及发展,与外周血主要抗原提呈细胞的HLA-Ⅱ类分子及HLA-DR分子表达无明显相关;BMFS患者Treg细胞比例与淋巴细胞HLA-Ⅱ分子表达呈正相关,而与淋巴细胞HLA-DR分子表达不相关,提示其发病机制尤其复杂。

Objective:HLA-Ⅱmolecules are directly involved in T-cell activation through antigen presenting cell expression.Regulatory T cells(Tregs)play an important role in regulating systemic immune responses.Anaemia is a common haematological disease with many causes.This study is to identify a possible correlation between HLA-Ⅱmolecular expression and Treg cell ratio.Methods:In this study,patients with autoimmune haemolytic anaemia(AIHA),bone marrow failure disease(BMFS),B-plasma cell tumour invading bone marrow,chronic anaemia secondary to infection,or liver and kidney diseases were studied to detect HLA-Ⅱmolecular expression and Treg cell ratio,and identify a possible correlation with anaemia severity.Results:There was no significant difference in the expression of HLA-Ⅱmolecules in lymphocytes and monocytes in all patients with anemia;the hemoglobin content in AIHA patients was negatively correlated with the proportion of Treg in peripheral blood;the proportion of Treg in BMFS patients was positively correlated with the expression of HLA-Ⅱin lymphocytes;the hemoglobin content of patients with B-plasma cell tumours invading the bone marrow was positively correlated with the expression of HLA-Ⅱand HLA-DR in lymphocytes;in patients with anemia of chronic disease secondary to infection or liver and kidney disease,the content of hemoglobin was negatively correlated with the expression of HLA-Ⅱand HLA-DR in monocytes,the proportion of Treg in peripheral blood was positively correlated with the expression of HLA-Ⅱand HLA-DR in lymphocytes.Conclusion:The monocyte immune response of patients with AIHA,BMFS,B-plasma cell tumour invading the bone marrow,and chronic anaemia secondary to infection or liver and kidney diseases was more active than that of healthy donors.The malignant lymphocytes of patients with B-plasma cell tumours involving bone marrow might realise immune escape and proliferation through low expression of HLA molecules.Anaemia secondary to infection or liver and kidney diseases might promote the activation of monocytes,and the Treg ratio might be related to the expression of HLA-Ⅱmolecules in lymphocytes.Treg reduction might be involved in the development and progression of AIHA and have no obvious correlation with the expression of HLA-Ⅱand HLA-DR molecules in the main antigen presenting cells.The proportion of Tregs in patients with BMFS positively correlated with HLA-Ⅱexpression in lymphocytes,but not with HLA-DR expression in lymphocytes,suggesting that its pathogenesis might be particularly complicated.