IFN-γ,caspase-3,LC3-II在原发性干燥综合征唇腺中的表达及其相关性

Expression and correlation of IFN-γ, caspase-3, LC3-II in labial glands of primary Sj?gren's syndrome

目的:检测干扰素γ(IFN-γ)、半胱氨酸天冬氨酸蛋白酶3(caspase-3)、微管相关蛋白1轻链3-I I (LC 3-I I)在原发性干燥综合征(p r i m a r ySj?g re n’ ss y n d ro m e, p S S)与非干燥综合征患者唇腺中的表达,探讨三者与唇腺灶性指数、血清抗核抗体滴度、补体及免疫球蛋白之间的关系,为进一步探索p SS发病机制提供依据。方法:收集p SS患者及怀疑p SS但最终排除诊断的患者的唇腺各19例,应用免疫组织化学检测组织样本中IFN-γ,caspase-3,LC3-II的表达,统计分析p SS患者及非p SS患者之间三者表达的差异性及三者与唇腺淋巴细胞浸润程度及自身免疫活化程度之间的相关性。结果:IFN-γ主要表达于唇腺中浸润的炎性细胞的细胞质中,caspase-3主要表达于唇腺腺泡上皮细胞及导管上皮细胞的细胞质中,LC3-II在炎性细胞和唇腺上皮细胞的细胞质中均有表达。IFN-γ,caspase-3,LC3-II(上皮细胞)、LC3-II(炎性细胞)在p SS及非p SS患者唇腺中的表达具有显著差异(均P<0.001)。IFN-γ在唇腺中的表达与caspase-3,LC3-II(上皮细胞)、LC3-II(炎性细胞)、灶性指数、抗核抗体滴度存在正相关性(r=0.549,0.822,0.757,0.762, 0.560,均P <0.001)。Caspase-3在唇腺中的表达除与I F N-γ之外,还与LC3-II (上皮细胞)、LC3-II(炎性细胞)、灶性指数、血清Ig A、类风湿因子(rheumatoid factor,RF)水平呈正相关(r=0.646,P<0.001;r=0.454,P=0.004;r=0.688,P<0.001;r=0.376,P=0.020;r=0.337,P=0.039)。LC3-II (上皮细胞)在唇腺中的表达除与IFN-γ, caspase-3之外,还与L C 3-I I (炎性细胞)、灶性指数、抗核抗体滴度呈正相关(r=0.800,P<0.001;r=0.788,P<0.001;r=0.467,P=0.003)。LC3-II (炎性细胞)在唇腺中的表达除与I F N-γ, caspase-3, LC3-II (上皮细胞)之外,还与灶性指数、抗核抗体滴度、类风湿因子呈正相关(r=0.727,P<0.001;r=0.459,P=0.004;r=0.410, P=0.011)。结论:I FN-γ, caspase-3, LC3-I I在pSS患者唇腺中高表达,三者之间存在相关性,且三者均与唇腺灶性指数及抗核抗体滴度呈正相关,提示II型干扰素通路的活化及唇腺上皮细胞的凋亡和自噬及炎性细胞自噬可能在p SS自身免疫活化中发挥重要作用,值得进一步探索。

Objective: To investigate the expression of IFN-γ, caspase-3, LC3-Ⅱ in primary Sjogren’s syndrome (pSS) patients’ labial gland and to explore the relationship between the three factors and the focus score of labial gland, serum antinuclear antibody titer, complement and immunoglobulin for providing a basis for further exploration of the pathogenesis of pSS. Methods: Labial glands of 19 patients with pSS and 19 patients suspected of pSS but ultimately excluded were collected. Using immunohistochemistry was used to detect the expression of IFN-γ, caspase-3 and LC3-Ⅱ in tissue samples. Statistical analysis of pSS patients and non-pSS patients between the expression of the three differences and the three with the degree of lymphocyte infiltration of the labial gland and the correlation between the degree of autoimmune activation. Results: IFN-γ is mainly expressed in the cytoplasm of inflammatory cells infiltrating in the labial glands. Caspase-3 is mainly expressed in the cytoplasm of labial gland acinar epithelial cells and ductal epithelial cells. LC3-Ⅱ is expressed in cytoplasm of both inflammatory cells and labial gland epithelial cells. The expressions of IFN-γ, caspase-3, LC3-Ⅱ(epithelial cells) and LC3-Ⅱ(inflammatory cells) in the labial glands of patients with pSS and non-pSS are significantly different (all P<0.001). The expression of IFN-γ in labial glands was positively correlated with caspase-3, LC3-Ⅱ(epithelial cells), LC3-Ⅱ(inflammatory cells), focus score and ANA titer (r=0.549, 0.822, 0.757, 0.762, 0.560, all P<0.001). In addition to IFN-γ, the expression of caspase-3 in labial gland is positively correlated with LC3-Ⅱ(epithelial cells), LC3-Ⅱ(inflammatory cells), focus score, serum IgA and RF levels (r=0.646, P<0.001;r=0.454, P=0.004;r=0.688, P<0.001;r=0.376, P=0.020;r=0.337, P=0.039). In addition to IFN-γ, caspase-3, the expression of LC3-Ⅱ(epithelial cell) in labial gland is positively correlated with LC3-Ⅱ(inflammatory cells), focus score and ANA titer (r=0.800, P<0.001;r=0.788, P<0.001;r=0.467, P=0.003). In addition to IFN-γ, caspase-3, LC3-Ⅱ(epithelial cells), the expression of LC3-Ⅱ(inflammatory cells) is positively correlated with focus score, ANA titer and RF (r=0.727, P<0.001;r=0.459, P=0.004;r=0.410, P=0.011). Conclusion: IFN-γ, caspase-3 and LC3-Ⅱ have high expression in the labial glands of pSS patients and there is a correlation between the three. The three are positively correlated with the focus score and ANA titer, which suggests the activation of type 2 interferon pathway, apoptosis and autophagy of lip gland epithelial cells, autophagy of inflammatory cells may play an important role in the activation of pSS autoimmunity, which is worth further exploring.