Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflammatory lesions of Sjogren's syndrome
Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflammatory lesions of Sjogren's syndrome
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DOI：
10.1002/art.23073
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发表时间：
2007-12-01
影响因子：
--
通讯作者：
Moutsopoulos, H. A.
中科院分区：
文献类型：
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作者：
Manoussakis, M. N.;Boiu, S.;Moutsopoulos, H. A.
Objective.目的探讨干燥综合征（SS）患者小涎腺（MSG）病变中浸润巨噬细胞、树突状细胞（DC）以及白细胞介素-18（IL-18）、IL-12的表达情况，并评估这些因素与疾病参数的关系。巨噬细胞、DC、T细胞、B细胞、proIL-18、成熟IL-18、.通过单标记和双标记免疫组化检测21例原发性SS患者（13/21检测IL-12）、7例继发性SS患者和9例疾病对照患者的MSG标本中的IL-12和IL-12。评估表达谱与各种疾病参数的相关性，包括淋巴瘤发展的不良预测因素。来自SS患者的MSG（但不是来自疾病对照）表现出巨噬细胞和DC的浸润增加、巨噬细胞的IL-18强表达（特别是在原发性SS中的富含B细胞的区域和生发中心样结构中）以及单核细胞浸润的IL-12表达。在原发性SS中，巨噬细胞的高浸润与SG增大相关（P = 0.01）。DC浸润率与巨噬细胞浸润率（P = 0.04）、SG增大（P = 0.03）和C4低补体血症（P = 0.05）呈正相关，与血清C4补体水平呈负相关（P = 0.001）。IL-18表达细胞的浸润率与活检病灶评分（P < 0.001）、巨噬细胞（P = 0.01）、DC（P = 0.01）和B细胞（P = 0.02）的较大浸润以及SG增大（P = 0.02）呈正相关，与血清C4补体水平呈负相关（P = 0.02）。IL-12表达细胞浸润率与IL-18表达细胞浸润率（P = 0.001）、活检病灶评分（P = 0.003）、SG增大（P = 0.01）呈负相关，与血清补体C4水平呈正相关（P = 0.05）。在原发性SS患者中，巨噬细胞和DC对SG的浸润以及IL-18和IL-12的表达似乎在浸润性损伤的扩展和组织中发挥积极作用，并与淋巴瘤发展的某些预测因子相关。
Objective. To evaluate the expression profile of infiltrating macrophages and dendritic cells (DCs) as well as of interleukin-18 (IL-18) and IL-12 in the minor salivary gland (MSG) lesions of patients with Sjogren's syndrome (SS), and to assess the relationship of these factors with disease parameters.Methods. Macrophages, DCs, T cells, B cells, proIL-18, mature IL-18,. and IL-12 were detected by single- and double-labeling immunohistochemistry in MSG specimens from 21 patients with primary SS (13 of 21 tested for IL-12), 7 patients with secondary SS, and 9 disease control patients. Expression profiles were assessed for correlations with various disease parameters, including adverse predictors of lymphoma development.Results. MSGs from patients with SS (but not from disease controls) manifested increased infiltration by macrophages and DCs, strong expression of IL-18 by macrophages (particularly in B cell-rich areas and in germinal center-like structures in primary SS), and expression of IL-12 by mononuclear cell infiltrates. In primary SS, high infiltration by macrophages correlated with SG enlargement (P = 0.01). The DC infiltration rate correlated positively with the macrophage infiltration rate (P = 0.04), occurrence of SG enlargement (P = 0.03), and presence of C4 hypocomplementemia (P = 0.05), and inversely with serum C4 complement levels (P = 0.001). The rate of infiltration by IL-I8-expressing cells correlated positively with biopsy focus scores (P < 0.001), larger infiltrates of macrophages (P = 0.01), DCs (P = 0.01), and B cells (P = 0.02), and SG enlargement (P = 0.02), and negatively with serum C4 complement levels (P = 0.02). The rate of infiltration by IL-12-expressing cells correlated inversely with that by IL-18-expressing cells (P = 0.001), biopsy focus scores (P = 0.003), and SG enlargement (P = 0.01), and positively with serum C4 complement levels (P = 0.05).Conclusion. In patients with primary SS, infiltration of the SG by macrophages and DCs and expression of IL-18 and IL-12 appear to play active roles in the expansion and organization of infiltrative injuries and have a correlation with certain predictors of lymphoma development.