重型再生障碍性贫血患者外周血自然杀伤细胞亚群百分比及功能变化
중형재생장애성빈혈환자외주혈자연살상세포아군백분비급공능변화
Percentages and functions of natural killer cell subsets in peripheral blood of patients with severe aplastic anemia
  • 万方数据
    中华医学杂志 중화의학잡지
    National Medical Journal of China
    2011年 16期 1084-1087 ,共4页

    李志赏%邵宗鸿%付蓉%王珺%李丽娟%张田%王化泉%吴玉红%阮二宝%宋嘉%瞿文%刘鸿%邢莉民%王晓明%梁勇%关晶%王国锦

    리지상%소종홍%부용%왕군%리려연%장전%왕화천%오옥홍%원이보%송가%구문%류홍%형리민%왕효명%량용%관정%왕국금

    贫血,再生障碍性%杀伤细胞,天然%穿孔素%颗粒酶β 貧血,再生障礙性%殺傷細胞,天然%穿孔素%顆粒酶β
    빈혈,재생장애성%살상세포,천연%천공소%과립매β
    Anemia,aplastic%Killer cells,natural%Perforin%Granzyme-β
    目的 分析重型再生障碍性贫血(SAA)患者免疫抑制治疗(IST)前、后外周血自然杀伤(NK)细胞亚群占淋巴细胞百分比、功能变化及其与造血功能相关性,探讨NK细胞在SAA发病机制中的作用.方法 用流式细胞术检测2010年4月至2010年12月天津医科大学总医院收治的12例初治(初治组)、30例IST后恢复(恢复组)的SAA患者的外周血NK细胞(CD3-CD56+/CD16+)及其亚群[CD3-CD56brightCD16-(CD56bright)、CD3-CD56dimCD16+(CD56dim)、CD3-CD56-CD16+]占淋巴细胞百分比、活化性受体(NKG2D和NKp46)、穿孔素、颗粒酶β表达,并与13名健康对照(对照组)比较;分析上述变化与外周血中性粒细胞比例(ANC%)、淋巴细胞比例、网织红细胞计数及骨髓造血功能(增生程度、粒系百分比、红系百分比、巨核细胞数量、淋系百分比)的相关性.结果 (1)初治组NK细胞、CD56bright细胞百分比(10.30%±6.08%、0.11%)均显著低于恢复组(16.47%±8.29%、0.68%,P＜0.05)和对照组(19.45%±6.88%、0.53%,均P＜0.05);初治组CD56dim细胞百分比(9.62%±6.04%)明显低于对照组(18.21%±7.16%,P＜0.05);恢复组CD3-CD56-CD16+细胞百分比(0.79%)显著高于初治组及对照组(0.37%、0.41%,均P＜0.05).(2)初治组与恢复组NK细胞NKp46、穿孔素表达[初治组(88.23%、64.97%±21.61%),恢复组(82.97%、66.14%±20.73%)]显著高于对照组(40.99%、42.11%±27.25%,均P＜0.05).(3)NK、CD56bright及CD3-CD56-CD16+细胞的百分比与SAA患者ANC%呈正相关(r分别为0.423、0.609、0.468,均P＜0.05),与骨髓粒系百分比呈正相关(r分别为0.357、0.517、0.434,均P＜0.05);NK、CD56bright、CD56dim和CD3-CD56-CD16+细胞的百分比与SAA患者骨髓增生程度呈正相关(r分别为0.455、0.412、0.404、0.451,均P＜0.05),与骨髓淋系百分比呈负相关(r分别为-0.522、-0.435、-0.411、-0.547,均P＜0.05);NK细胞NKG2D、NKp46、穿孔素、颗粒酶β表达与各造血指标无相关性(均P＞0.05).结论 SAA患者外周血NK细胞、CD56bright、CD56dim亚群占淋巴细胞百分比降低及穿孔素途径增强可能引起免疫耐受被破坏、T细胞功能亢进而导致造血功能衰竭.
    목적 분석중형재생장애성빈혈(SAA)환자면역억제치료(IST)전、후외주혈자연살상(NK)세포아군점림파세포백분비、공능변화급기여조혈공능상관성,탐토NK세포재SAA발병궤제중적작용.방법 용류식세포술검측2010년4월지2010년12월천진의과대학총의원수치적12례초치(초치조)、30례IST후회복(회복조)적SAA환자적외주혈NK세포(CD3-CD56+/CD16+)급기아군[CD3-CD56brightCD16-(CD56bright)、CD3-CD56dimCD16+(CD56dim)、CD3-CD56-CD16+]점림파세포백분비、활화성수체(NKG2D화NKp46)、천공소、과립매β표체,병여13명건강대조(대조조)비교;분석상술변화여외주혈중성립세포비례(ANC%)、림파세포비례、망직홍세포계수급골수조혈공능(증생정도、립계백분비、홍계백분비、거핵세포수량、림계백분비)적상관성.결과 (1)초치조NK세포、CD56bright세포백분비(10.30%±6.08%、0.11%)균현저저우회복조(16.47%±8.29%、0.68%,P＜0.05)화대조조(19.45%±6.88%、0.53%,균P＜0.05);초치조CD56dim세포백분비(9.62%±6.04%)명현저우대조조(18.21%±7.16%,P＜0.05);회복조CD3-CD56-CD16+세포백분비(0.79%)현저고우초치조급대조조(0.37%、0.41%,균P＜0.05).(2)초치조여회복조NK세포NKp46、천공소표체[초치조(88.23%、64.97%±21.61%),회복조(82.97%、66.14%±20.73%)]현저고우대조조(40.99%、42.11%±27.25%,균P＜0.05).(3)NK、CD56bright급CD3-CD56-CD16+세포적백분비여SAA환자ANC%정정상관(r분별위0.423、0.609、0.468,균P＜0.05),여골수립계백분비정정상관(r분별위0.357、0.517、0.434,균P＜0.05);NK、CD56bright、CD56dim화CD3-CD56-CD16+세포적백분비여SAA환자골수증생정도정정상관(r분별위0.455、0.412、0.404、0.451,균P＜0.05),여골수림계백분비정부상관(r분별위-0.522、-0.435、-0.411、-0.547,균P＜0.05);NK세포NKG2D、NKp46、천공소、과립매β표체여각조혈지표무상관성(균P＞0.05).결론 SAA환자외주혈NK세포、CD56bright、CD56dim아군점림파세포백분비강저급천공소도경증강가능인기면역내수피파배、T세포공능항진이도치조혈공능쇠갈.
    Objective To analyze the percentage and functional changes of natural killer(NK)cell subsets in peripheral blood of severe aplastic anemia(SAA)patients before and after immunosuppressive therapy(IST)so as to evaluate the relationships between these changes and hematopoietic functions and explore the role of NK cells in the pathogenesis of SAA.Methods By flow cytometry,the percentages of NK cells(CD3-CD56+/CD16+)and its subsets[CD3-CD56brightCD16-(CD56bright),CD3-CD56dimCD16+(CD56dim),CD3-CD56-CD16+]in peripheral blood lymphocytes were detected in 12 untreated patients,30 recovered patients and 13 normal controls respectively from April 2010 to December 2010 in our hospital.NK cells activating receptors(NKG2D and NKp46),pofforin and granzyme-β of patients and normal controls were also detected.The correlation between these changes and hematopoietic functions,including the percentages of neutrophil granulocyte(ANC%),lymphocyte and reticulocyte absolute value in peripheral blood,and hyperplasia degree,percentage of granulocytes,erythrocytes,lymphocytes and megakaryocytes absolute value in bone marrow were evaluated.Results (1)The percentages of NK cells (10.30% ± 6.08%)and CD56 bright cells(0.11%)in untreated patients were significantly lower than those of recovered patients(16.47% ± 8.29%,0.68%,both P ＜0.05)or normal controls(19.45% ±6.88%,0.53%,both P ＜0.05).The percentage of CD56dim cells in untreated patients was significantly lower than that of normal controls(9.62% ±6.04% vs 18.21% ±7.16%,P ＜0.05).The percentage of CD3 CD56 CD16 + cells was significantly higher in recovered patients than that of untreated patients or normal controls(0.79% vs 0.37%,0.41%,both P＜0.05).(2)The expression of NKp46 and pefforin of NK cells in untreated(88.23%,64.97% ± 21.61%)and recovered patients(82.97%,66.14% ±20.73%)were significantly higher than those of healthy controls(40.99%,42.11% ±27.25%,all P ＜0.05).(3)The percentage of NK CD56bright and CD3-CD56-CD16+ cells of patients was positively correlated with ANC%(r=0.423,0.609,0.468 respectively,all P＜0.05)and the percentage of granulocytes in bone marrow(r=0.357,0.517,0.434 respectively,all P＜0.05).The percentages of NK,CD56bight,CD56dim and CD3-CD56-CD16+ cells were positively correlated with the hyperplasic degree of bone marrow(r=0.455,0.412,0.404,0.451 respectively,all P＜0.05),but they were negatively correlated with the percentage of lymphocytes in bone marrow(r =-0.522,-0.435,-0.411,-0.547 respectively,all P ＜0.05).The expression of NKG2D,NKp46,pefforin and granzyme-β of NK cells had no correlation with hematopoiesis(all P＞0.05).Conclusion The lowered percentage of NK CD56bright,CD56dim cells and a higher expression of pefforin may cause the over-function of T lymphocytes and thus lead to hematopoietic failure in SAA.
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