Salomonsson Stina, Jonsson Malin V, Skarstein Kathrine, Brokstad Karl A, Hjelmström Peter, Wahren-Herlenius Marie, Jonsson Roland
Karolinska Institutet, Stockholm, Sweden.
Arthritis Rheum. 2003 Nov;48(11):3187-201. doi: 10.1002/art.11311.
To investigate functional properties of the germinal center (GC)-like structures observed in salivary glands of patients with Sjögren's syndrome (SS) and to determine the frequency with which such structures develop.
Hematoxylin and eosin-stained sections from 165 minor salivary gland biopsy samples were screened for GC-like structures. Expression of markers for GCs (CD3, CD20, Ki-67, CD35, CD31), adhesion molecules (intercellular adhesion molecule 1, lymphocyte function-associated antigen 1, vascular cell adhesion molecule 1, very late activation antigen 4), chemokines (CXCL13, CCL21, CXCL12), and production of autoantibodies (anti-Ro/SSA and anti-La/SSB) was investigated by immunohistochemistry. Apoptosis was investigated by TUNEL staining.
GC-like structures were observed in 28 of 165 patients (17%). When GCs were defined as T and B cell aggregates with proliferating cells with a network of follicular dendritic cells and activated endothelial cells, such microenvironments were found in all patients in whom structures with GC-like morphology were observed. The defined microenvironments were not found in patients without apparent GC-like structures. The GCs formed within the target tissue showed functional features with production of autoantibodies (anti-Ro/SSA and anti-La/SSB) and apoptotic events (by TUNEL staining), and the local production of anti-Ro/SSA and anti-La/SSB autoantibodies was significantly increased (P = 0.04) in patients with GC development.
Lymphoid neogenesis and functional ectopic GC formation take place in salivary glands of a subset of patients with SS. Our data suggest that the ectopic secondary lymphoid follicles contain all elements needed for driving the autoimmune response. Our findings underscore a key role for the target organ in recruitment of inflammatory cells and propagation of the disease process.
研究干燥综合征（SS）患者唾液腺中观察到的生发中心（GC）样结构的功能特性，并确定此类结构形成的频率。
对165份小唾液腺活检样本的苏木精-伊红染色切片进行GC样结构筛查。通过免疫组织化学研究GC标志物（CD3、CD20、Ki-67、CD35、CD31）、黏附分子（细胞间黏附分子1、淋巴细胞功能相关抗原1、血管细胞黏附分子1、极迟活化抗原4）、趋化因子（CXCL13、CCL21、CXCL12）的表达以及自身抗体（抗Ro/SSA和抗La/SSB）的产生。通过TUNEL染色研究细胞凋亡。
165例患者中有28例（17%）观察到GC样结构。当将GC定义为具有增殖细胞、滤泡树突状细胞网络和活化内皮细胞的T细胞和B细胞聚集物时，在所有观察到具有GC样形态结构的患者中均发现了此类微环境。在没有明显GC样结构的患者中未发现所定义的微环境。在靶组织内形成的GC表现出产生自身抗体（抗Ro/SSA和抗La/SSB）和凋亡事件（通过TUNEL染色）的功能特征，并且在发生GC的患者中抗Ro/SSA和抗La/SSB自身抗体的局部产生显著增加（P = 0.04）。
在一部分SS患者的唾液腺中发生了淋巴新生和功能性异位GC形成。我们的数据表明，异位二级淋巴滤泡包含驱动自身免疫反应所需的所有要素。我们的发现强调了靶器官在募集炎症细胞和疾病过程传播中的关键作用。
