Elevated serum BAFF levels in patients with sarcoidosis: association with disease activity
Elevated serum BAFF levels in patients with sarcoidosis: association with disease activity
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DOI：
10.1093/rheumatology/ket186
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发表时间：
2013-09-01
期刊：
影响因子：
5.5
通讯作者：
Okamoto, Hiroyuki
中科院分区：
文献类型：
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作者：
Ueda-Hayakawa, Ikuko;Tanimura, Hirotsugu;Okamoto, Hiroyuki
Objective.本研究的目的是确定结节病患者血清B细胞活化因子（BAFF）水平及其与临床的关系。采用酶联免疫吸附试验（ELISA）检测了37例患者和21名健康受试者的血清BAFF水平。同时检测结节病患者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。流式细胞术分析外周血B细胞亚群。用免疫组化法检测BAFF在皮肤肉芽肿中的表达。以HEp-2细胞为底物，间接免疫荧光法测定抗核抗体。与健康对照组相比，结节病患者血清BAFF水平显著升高。血清BAFF升高的患者皮肤和眼睛受累的频率显著高于血清BAFF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BAFF抗体的免疫染色显示肉芽肿上皮样细胞表达BAFF。在体外，IFN-γ诱导单核细胞上的膜结合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，记忆B细胞和浆母细胞减少。26例结节病患者ANA阳性17例（65%）。血清BAFF水平可用作结节病患者疾病活动性的替代标志物。BAFF增高可能与结节病的发病机制有关。
Objective. 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-gamma levels in sarcoidosis patients were also measured. Isolated monocytes cultured with IFN-gamma, 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.Results. 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-gamma. Immunostaining of anti-BAFF in the skin revealed BAFF expression by epithelioid cells of granuloma. In vitro, IFN-gamma induced membrane-bound BAFF expression on monocytes and secretion of soluble BAFF by isolated monocytes. In the peripheral blood, sarcoidosis patients showed increased naive B cells with a reciprocal decrease in memory B cells and plasmablasts. Seventeen of 26 (65%) sarcoidosis patients exhibited ANA positivity.Conclusion. 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.