Akin E, Aversa J, Steere A C
Division of Rheumatology/Immunology, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA.
Infect Immun. 2001 Mar;69(3):1774-80. doi: 10.1128/IAI.69.3.1774-1780.2001.
The expression of adhesion molecules in synovium in patients with Lyme arthritis is surely critical in the control of Borrelia burgdorferi infection but may also have pathologic consequences. For example, molecular mimicry between a dominant T-cell epitope of B. burgdorferi outer surface protein A and an adhesion molecule, human lymphocyte function-associated antigen 1 (LFA-1), has been implicated in the pathogenesis of treatment-resistant Lyme arthritis. Using immunohistochemical methods, we examined synovial samples for expression of adhesion molecules in 29 patients with treatment-resistant Lyme arthritis and in 15 patients with rheumatoid arthritis or chronic inflammatory monoarthritis. In Lyme arthritis synovia, endothelial cells showed intense expression of P-selectin and vascular adhesion protein-1 (VAP-1). Expression of LFA-1 was also intense on infiltrating cells, particularly in lymphoid aggregates, and intercellular adhesion molecule-1 (ICAM-1) was markedly expressed on synovial lining and endothelial and infiltrating cells. Moderate expression of vascular cell adhesion molecule-1 (VCAM-1) was seen on synovial lining and endothelial cells, and mild expression of its ligand, very late antigen-4, was apparent in perivascular lymphoid infiltrates. Except for lesser expression of VCAM-1 in Lyme synovia, the levels of expression of these adhesion molecules were similar in the three patient groups. We conclude that certain adhesion molecules, including ICAM-1 and LFA-1, are expressed intensely in the synovia of patients with Lyme arthritis. Upregulation of LFA-1 on lymphocytes in this lesion may be critical in the pathogenesis of treatment-resistant Lyme arthritis.
莱姆关节炎患者滑膜中黏附分子的表达对于控制伯氏疏螺旋体感染肯定至关重要,但也可能产生病理后果。例如,伯氏疏螺旋体外膜蛋白A的一个主要T细胞表位与人淋巴细胞功能相关抗原1(LFA-1,一种黏附分子)之间的分子模拟,被认为与难治性莱姆关节炎的发病机制有关。我们采用免疫组化方法,检测了29例难治性莱姆关节炎患者以及15例类风湿关节炎或慢性炎症性单关节炎患者滑膜样本中黏附分子的表达情况。在莱姆关节炎滑膜中,内皮细胞显示P-选择素和血管黏附蛋白-1(VAP-1)的强烈表达。LFA-1在浸润细胞上的表达也很强烈,尤其是在淋巴样聚集物中,细胞间黏附分子-1(ICAM-1)在滑膜衬里、内皮细胞和浸润细胞上均有明显表达。滑膜衬里和内皮细胞上可见血管细胞黏附分子-1(VCAM-1)的中度表达,其配体极迟抗原-4在血管周围淋巴浸润中有轻度表达。除莱姆病滑膜中VCAM-1表达较少外,这三种患者组中这些黏附分子的表达水平相似。我们得出结论,某些黏附分子,包括ICAM-1和LFA-1,在莱姆关节炎患者的滑膜中强烈表达。该病变中淋巴细胞上LFA-1的上调可能在难治性莱姆关节炎的发病机制中起关键作用。