CAJ | 학술논문

目的研究巨噬细胞活化综合征(MAS)患儿自然杀伤(NK)细胞功能变化.方法采用流式细胞术检测12例健康对照、12例幼年特发性关节炎全身型(SoJIA)和12例MAS患儿急性期和治疗后5d和3个月外周血中NK细胞数及其杀伤活性、穿孔素、颗粒酶B、γ干扰素(IFN-y)和肿瘤坏死因子α(TNF-α)的表达.结果与健康对照和SoJIA对照比较,MAS治疗前和治疗后5dNK细胞计数、杀伤活性、穿孔素和颗粒酶B降低(P＜0.05),治疗前分泌IFN-γ、TNF-α增加(P＜0.05).治疗后3个月NK细胞计数和分泌IFN-y、TNF-α与健康对照无统计学差异(P＞0.05),但NK细胞杀伤活性、穿孔素和颗粒酶B表达仍低于健康对照和SoJIA对照(P＜0.05).结论 NK细胞杀伤活性低下和分泌IFN-γ、TNF-α增加参与MAS发生.免疫治疗逐渐恢复NK细胞数目,减少IFN-γ和TNF-α分泌,但杀伤活性和穿孔素、颗粒酶B表达降低是MAS患儿持续存在的NK细胞功能特点.
목적 연구거서세포활화종합정(MAS)환인자연살상(NK)세포공능변화.방법 채용류식세포술검측12례건강대조、12례유년특발성관절염전신형(SoJIA)화12례MAS환인급성기화치료후5d화3개월외주혈중NK세포수급기살상활성、천공소、과립매B、γ간우소(IFN-y)화종류배사인자α(TNF-α)적표체.결과 여건강대조화SoJIA대조비교,MAS치료전화치료후5dNK세포계수、살상활성、천공소화과립매B강저(P＜0.05),치료전분비IFN-γ、TNF-α증가(P＜0.05).치료후3개월NK세포계수화분비IFN-y、TNF-α여건강대조무통계학차이(P＞0.05),단NK세포살상활성、천공소화과립매B표체잉저우건강대조화SoJIA대조(P＜0.05).결론 NK세포살상활성저하화분비IFN-γ、TNF-α증가삼여MAS발생.면역치료축점회복NK세포수목,감소IFN-γ화TNF-α분비,단살상활성화천공소、과립매B표체강저시MAS환인지속존재적NK세포공능특점.
Objective To analyze the functional alteration of natural killer (NK) cells from patients with macrophage activation syndrome (MAS) in active phase and after treatment.Methods Peripheral blood samples were collected from 12 healthy subjects,12 patients with systemic onset juvenile rheumatoid arthritis (SoJIA) but without an episode of MAS and 12 patients with MAS.Flow cytometry analysis was performed to detect NK cells and their expression of perforin,granzyme B,interferon (IFN)-γand tumour necrosis factor (TNF)-α.The cytotoxicity of NK cells to K562 cell was also analyzed.All of the patients with MAS were diagnozed by clinical features and the pathologic examination of hemophagocytosis in bone marrow.The function of NK cells were analyzed before any treatment and on the fifth day as well as in third month after treatment with glucocorticoid,intravenous immunoglobulin and/or cyclosporin A.Results Compared with healthy subjects and patients with SoJIA,patients with MAS had lower NK cell counts,reduced cytotoxicity and decreased expression of perforin and granzyme B before or on the fifth day after treatment (P＜0.05).However,increased production of IFN-γ and TNF-α by NK cells were observed (P＜ 0.05).In the third month after treatment,the cytotoxicity of NK cells and the expression of perforin and granzyme B in patients with MAS were lower than those in healthy subjects and patients with SoJIA (P＜ 0.05),but no statistically significant differences with NK cell counts and production of IFN-γand TNF-α were observed beween the patients with MAS and healthy subjects (P＞0.05).Conclusion NK cells from patients with active MAS were characterized by reduced cytotoxicity and enhanced production of IFN-γ and TNF-α.Upon medical treatment,the number of NK cells in patients with MAS were up-regulated and their production of IFN-γand TNF-α were down-regulated.However,the cytotoxicity of NK cells and the expression of perforin and granzyme B were not affected.Reduced cytotoxicity and decreased production of perforin and granzyme B with NK cells might be the durative features for the patients with MAS.