Department of Dermatology, Kansai Medical University, Hirakata, Osaka, Japan.
Rheumatology (Oxford). 2013 Sep;52(9):1658-66. doi: 10.1093/rheumatology/ket186. Epub 2013 May 17.
The purpose of this study was to determine serum levels of B-cell-activating factor (BAFF) and its clinical association in patients with sarcoidosis. METHODS; Serum levels of BAFF from 37 patients and 21 healthy subjects were examined by ELISA. Serum angiotensin-converting enzyme (ACE), lysozyme and IFN-γ levels in sarcoidosis patients were also measured. Isolated monocytes cultured with IFN-γ, IL-4 or IL-10 and their expression of membrane and soluble BAFF were analysed by flow cytometry or ELISA. Peripheral B cell subsets were analysed by flow cytometry. BAFF expression in the granuloma of the skin was examined by immunohistochemistry. ANAs were determined by indirect IF using HEp-2 cells as a substrate.
Serum BAFF levels were significantly elevated in sarcoidosis patients when compared with healthy controls. The frequency of skin and eye involvement was significantly higher in patients with elevated serum BAFF than in patients with normal levels. Serum BAFF levels were correlated with serum levels of ACE, lysozyme and IFN-γ. Immunostaining of anti-BAFF in the skin revealed BAFF expression by epithelioid cells of granuloma. In vitro, IFN-γ induced membrane-bound BAFF expression on monocytes and secretion of soluble BAFF by isolated monocytes. In the peripheral blood, sarcoidosis patients showed increased naïve B cells with a reciprocal decrease in memory B cells and plasmablasts. Seventeen of 26 (65%) sarcoidosis patients exhibited ANA positivity.
Serum BAFF levels can be used as a surrogate marker of disease activity in sarcoidosis patients. Increased BAFF may be related to the pathogenesis of sarcoidosis.
本研究旨在确定 B 细胞激活因子(BAFF)在结节病患者中的血清水平及其临床相关性。
通过 ELISA 检测 37 例患者和 21 例健康对照者的血清 BAFF 水平。还测量了结节病患者的血清血管紧张素转换酶(ACE)、溶菌酶和 IFN-γ水平。用 IFN-γ、IL-4 或 IL-10 培养分离的单核细胞,并通过流式细胞术或 ELISA 分析其膜和可溶性 BAFF 的表达。通过流式细胞术分析外周 B 细胞亚群。通过免疫组织化学法检测皮肤肉芽肿中的 BAFF 表达。通过间接免疫荧光法(IF)使用 HEp-2 细胞作为底物测定 ANA。
与健康对照组相比,结节病患者的血清 BAFF 水平显著升高。血清 BAFF 水平升高的患者皮肤和眼部受累的频率明显高于 BAFF 水平正常的患者。血清 BAFF 水平与血清 ACE、溶菌酶和 IFN-γ水平相关。皮肤中抗 BAFF 的免疫染色显示肉芽肿的上皮样细胞表达 BAFF。在体外,IFN-γ诱导单核细胞表面结合的 BAFF 表达和分离的单核细胞分泌可溶性 BAFF。在外周血中,结节病患者表现出幼稚 B 细胞增加,而记忆 B 细胞和浆母细胞减少。26 例结节病患者中的 17 例(65%)出现 ANA 阳性。
血清 BAFF 水平可作为结节病患者疾病活动的替代标志物。BAFF 的增加可能与结节病的发病机制有关。