浆细胞样树突状细胞及T淋巴细胞相关细胞因子在原发性干燥综合征患者唇腺组织中的检测与临床意义

doi:10.3877/cma.j.issn.1674-0785.2019.06.008

目的

初步探讨浆细胞样树突状细胞（pDC）在原发性干燥综合征（pSS）患者唇腺组织炎性破坏中的作用及临床意义。

方法

收集苏州市昆山第一人民医院2015年1月至2017年8月确诊为pSS的患者唇腺组织39例作为研究组，不符合干燥综合征诊断的口干患者19例作为对照组。采用免疫荧光抗体标记法检测2组唇腺组织中pDC及T淋巴细胞相关因子γ-干扰素（IFN-γ）的表达情况，采用免疫细胞定量法计数pDC及IFN-γ表达情况，采用秩和检验比较2组pDC及IFN-γ表达的差异，采用Spearman双变量相关分析分析其与淋巴细胞灶指数及临床指标的相关性。

结果

pSS患者唇腺组织中可见大量pDC细胞浸润，研究组pDC计数为103（76，203）个/高倍视野，对照组为46（39，50）个/高倍视野，2组比较差异具有统计学意义（Z=-5.602，P<0.001）；IFN-γ可见异常高表达，研究组IFN-γ计数为174（137，214）个/高倍视野，对照组为116（112，120）个/高倍视野，2组比较差异具有统计学意义（Z=-5.783，P<0.001）；pDC计数与淋巴细胞灶指数呈正相关（r=0.810，P<0.001），与IFN-γ呈正相关（r=0.894，P<0.001），与pSS疾病活动指标（免疫球蛋白、血沉、C反应蛋白和ESSDAI评分等）无明显相关性（P>0.05）。

结论

pSS患者唇腺组织大量的pDC浸润及淋巴细胞因子的异常高表达均与淋巴细胞浸润程度密切相关，且pDC可能通过激活淋巴细胞免疫应答产生相关细胞因子参与唇腺组织局部炎性破坏，故检测唇腺组织中pDC可能有助于pSS的临床病理诊断。

关键词: 原发性干燥综合征, 浆细胞样树突状细胞, γ-干扰素, 免疫荧光标记, 激光扫描共聚焦显微镜

Objective

To determine the expression of plasmacytoid dendritic cells and interferon-gama (IFN-γ) in the labial gland tissue of patients with primary Sjogren′s syndrome (pSS) to investigate the role of pDC in the pathogenesis of pSS and their significance.

Methods

Gland tissue samples were collected from 39 patients with pSS and 19 patients with dry mouth who did not meet the diagnostic criteria for pSS. pDC and IFN-γ were determined by fluorescent antibody technique to assess the association between pDC and lymphocyte focal index as well as the association between pDC and clinical indexes of pSS patients. The difference between the two groups of data was measured by the rank-sum test, and Spearman bivariate correlation analysis was performed to examine the correlation between variables.

Results

A large number of pDC cells were observed in the lip gland tissue of patients with pSS, and the count of pDC in the study group was significantly higher than that of the control group [103 (76, 203) vs 46 (39, 50), Z=-5.602, P<0.001)]. There was unusually high expression of IFN-γ in the study group, and the count of IFN-γ positive cells was also significantly higher in the study group than in the control group [174 (137, 214) vs 116 (112, 120), Z=-5.783, P<0.001)]. There was a positive correlation between pDC counts and lymphocyte focal index (r=0.810, P<0.001) as well as between pDC counts and the expression of IFN-γ (r=0.894, P<0.001), although there was no significant correlation between pDC and clinical indexes (P>0.05).

Conclusion

Both massive infiltration of pDC and overexpression of interferon are closely correlated with lymphocytic infiltration in labial gland tissue of patients with pSS. pDC are involved in the immune injury of labial gland tissue. Detection of pDC may be conducive to early pathological diagnosis of pSS.

Key words: Primary Sjogren′s syndrome, Plasmacytoid dendritic cells, Interferon gama, Immunofluorescent labeling, Laser confocal

表1 研究组与对照组、抗SSA/SSB抗体阳性组与抗体均阴性组的pDC、IFN-γ表达计数的差异（个/高倍视野）

组别	例数	pDC计数	IFN-γ
研究组	39	103（76，203）	174（137，214）
对照组	19	46（39，50）	116（112，120）
Z值	?	-5.602	-5.783
P值	?	<0.001	<0.001
抗SSA/SSB抗体阳性组	26	101（77，181）	151（141.5，203.5）
抗SSA/SSB抗体阴性组	13	169（72.5，216）	196（131.5，224）
Z值	?	-1.028	-0.820
P值	?	0.304	0.412

表1 研究组与对照组、抗SSA/SSB抗体阳性组与抗体均阴性组的pDC、IFN-γ表达计数的差异（个/高倍视野）

组别	例数	pDC计数	IFN-γ
研究组	39	103（76，203）	174（137，214）
对照组	19	46（39，50）	116（112，120）
Z值	?	-5.602	-5.783
P值	?	<0.001	<0.001
抗SSA/SSB抗体阳性组	26	101（77，181）	151（141.5，203.5）
抗SSA/SSB抗体阴性组	13	169（72.5，216）	196（131.5，224）
Z值	?	-1.028	-0.820
P值	?	0.304	0.412

图3~4 对照组与研究组IFN-γ阳性细胞染色图（荧光抗体标记法，×400倍）图3为对照组，图4为研究组

表2 pSS患者唇腺组织中pDC细胞定量计数与IFN-γ及各临床指标的相关性

相关指标	淋巴细胞灶数	IFN-γ	ESSDAI	血沉	C反应蛋白	IgA	IgG	ANA
r值	0.810	0.894	0.235	0.182	-0.021	0.079	0.063	0.114
P值	<0.001	<0.001	0.150	0.275	0.913	0.780	0.804	0.496

表2 pSS患者唇腺组织中pDC细胞定量计数与IFN-γ及各临床指标的相关性

相关指标	淋巴细胞灶数	IFN-γ	ESSDAI	血沉	C反应蛋白	IgA	IgG	ANA
r值	0.810	0.894	0.235	0.182	-0.021	0.079	0.063	0.114
P值	<0.001	<0.001	0.150	0.275	0.913	0.780	0.804	0.496

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Clinical significance of expression of plasmacytoid dendritic cells and interferon-γ in labial gland tissue of patients with Sjogren′s syndrome

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Clinical significance of expression of plasmacytoid dendritic cells and interferon-γ in labial gland tissue of patients with Sjogren′s syndrome