CD14基因多态性与严重烧伤患者预后及人白细胞抗原DR表达的相关性研究

The correlation between CD14 gene polymorphism and prognosis and human leukocyte antigen DR expression in patients with major burns

目的探讨CD14基因多态性与大面积烧伤患者预后及人白细胞抗原-DR(HLA- DR)表达的相关程度。方法采集103例烧伤体表总面积＞30%患者血标本,通过聚合酶链反应-限制性片断长度多态性方法检测CD14-159C/T基因多态性。采用流式细胞技术(使用QuantiBRITE^TM) Anti-HLA-DR PE~*/Anti-Monocyte PerCP-Cy5．5单克隆抗体)对患者烧伤后1,3,5,7,14,21,28 d单核细胞表面HLA-DR抗体的结合量进行定量分析。结果在特重度烧伤患者中(71例),CD14基因多态性携带TY型的患者脓毒症发生率(72．2%)及死亡率(50．0%)高于TC基因型(分别为60．9%、23．9%)和CC基因型(分别为57．1%、28．6%)(P＜0．05)。特重度烧伤患者中脓毒症组(45例)HLA-DR结合抗体量伤后逐步下降,而非脓毒症(26例)组伤后第5天以后持续升高,伤后第3,7,14,21,28 d两组比较,差异有统计学意义(P＜0．01)。伤后3,14,21 d,CC纯合子患者HLA-DR抗体结合量均明显高于TY纯合子(P＜0．05),而与TC型比较,差异无统计学意义(P＞0．05)。结论CD14-159C/T多态性与严重烧伤后并发脓毒症及患者预后有关,TT纯合子可能是特重烧伤后机体免疫应答反应异常的相关“易感基因”之一。

Objective To investigate the correlation between CD14 gene polymorphism and prognosis and human leukocyte antigen DR （HLA-DR） expression in patients with major burns. Methods One hundred and three patients with major burns （ TBSA 〉 30% ） were enrolled in this study. CD14- 159C/T gene polymorphism was determined by polymerase chain reaction and subsequent restriction enzyme digestion of the polymerase chain products. The amounts of binding HLA-DR in mononuclear cell surface of burned patients were quantitated by flow cytometry （using monoclonal antibody, QuantiBRITETM Anti-HLA-DR PE＊/Anti-Monocyte PerCP-CyS. 5） on postburn days 1, 3, 5, 7, 14, 21 and 28. Results Among severely burned patients （TBSA 〉 50%, 71 cases）, the incidence of sepsis （72.2%） and mortality （50%） were significantly higher in patients with CD14 homozygous for the T allele （TT） than those with genotype TC （60.9% and 23.9% ） and genotype CC（57.1% and 28.6% ） （ P 〈 0.05 ）, respectively. The amount of binding HLA-DR was decreased gradually in the septic group （45 cases）, but increased in the non-septic group （26 cases） on postburn day 5, and became significantly different between the two groups on postburn days 3, 7, 14, 21 and 28 （P 〈0.01 ）. The amount of binding HLA-DR was markedly higher in patients with homozygous C than in patients with homozygous T （P〈0.01） on postburn days 3, 14 and 21, but no difference was found in patients with genotype TC （ P 〉 0.05 ）. Conclusion CD14 - 159C/T polymorphism is correlated with development of septic complications in patients with major burns and their prognosis. The homozygous T of CD14 might be one of the “predisposing genes” in host immune response after severe burns.