干燥综合征患者唇腺组织与外周血B淋巴细胞活化因子及其受体的表达及意义

Expression of BAFF/BAFF-R in labial salivary glands/peripheral blood and its significance in Sjoegren＇s syndrome patients

目的检测原发性干燥综合征（pSS）及重叠其他结缔组织病的干燥综合征（SS）患者外周血B淋巴细胞活化因子（BAFF）和外周血B淋巴细胞／唇腺组织中BAFF受体（BAFF—R）的表达，进一步观察和研究BAFF在SS发病过程中的作用，并探讨将唇腺组织BAFF—R水平检测作为SS病理诊断指标的可能性。方法选取确诊pSS患者和与类风湿关节炎（RA）或系统性红斑狼疮（SLE）重叠的SS患者唇腺组织及外周血样本各15例，并选择15例非SS颌面部手术患者的正常唇腺组织及外周血作为对照。同步采用免疫组织化学技术检测唇腺组织BAFF—R表达情况，以流式细胞术检测外周血CD19^＋B淋巴细胞表面BAFF—R的表达水平，采用酶联免疫吸附试验（ELISA）法测定外周血清中可溶性BAFF的水平。采用，检验、Fisher确切概率法、单因素方差分析、LSD—t检验进行统计学处理。结果与对照组15例唇腺组织BAFF—R弱阳性着色相比，13例占87％的pSS患者唇腺组织中BAFF—R特异性染色呈强阳性；SS患者外周血中CD19^＋B淋巴细胞膜表面BAFF—R表达和血清中可溶性BAFF均高于对照组[（21．4±4．6）％与（4．0±1．6）％，P〈0．01；（7．5±2．3）mg/ml与（2．0±0．8）ng/ml，P〈0．01]。而15例与RA／SLE重叠的SS患者，其唇腺组织的BAFF—R的表达占75％，外周血CD19^＋B淋巴细胞膜表面BAFF—R的表达为（23．3±5．0）％，其血清中可溶性BAFF的表达为（7．8±1．9）ng/ml均高于对照组（P值均〈0．01），但与pSS组相比差异无统计学意义（P值均〉0．05）。结论SS患者唇腺组织与外周血中B淋巴细胞膜表面BAFF—R以及血清可溶性BAFF的表达水平均上调，可能通过激活自身反应性B淋巴细胞参与SS的发病过程；检测唇腺组织B淋巴细胞膜表面BAFF—R可能有助于SS的诊断和疾病活动的判定。

Objective To clarify the role of BAFF （B-cell activating factor from TNF family, BAFF） in the pathogenesis of pSS （primary Sjogren＇s syndrome, pSS） and SS overlapped with other connective diseases, and explore the diagnostic value of BAFF-R （BAFF Receptor, BAFF-R） for SS by detecting the expression of BAFF in serum and BAFF-R on peripheral B cells/labial salivary glands from SS patients. Methods The expression of BAFF-R was detected in labial salivary glands and CD19^＋ B cells in the peripheral blood from 15 pSS patients and 15 SS overlapped with rheumatoid arthritis （RA） / systemic lupus erythematosus （SLE） by immunohistoehemistry and flow cytometry respectively. The concentration of the soluble BAFF in serum was detected by ELISA. The labial salivary glands and the peripheral blood from 15 healthy donors served as controls. Chi-square test, Fisher exact test, oneway-ANOVA and LSD-t test for statistical anglysis. Results BAFF-R was strongly stained on labial salivary glands from 13/15 pSS-paients （87%）, while weakly stained on those of the controls. BAFF-R was also expressed significantly higher in CD19^＋ B ceils from patients [（21.4±4.6）% vs （4.0±1.6）%, P〈0.01]. Similar to these, soluble BAFF was highly detected in sera of patients than that of the controls [（2.0 ± 0.8） ng/ml vs （7.5±2.3） ng/ml, P〈 0.01 ]. AS for 15 SS overlapped with RA/SLE-patients, the expression of BAFF-R in labial salivary （75.0%） and in CD19^＋B cells （23.3±5.0）%, and the secretion of soluble BAFF in sera （7.8±1.9） ng/ml were all significantly higher than that of controls （P〈0.01）, while similar to that of pSS patients （P〉0.05）. Conelusion Our study further clarifies that up-regulation of BAFF and BAFF-R may play an important role in the pathogenesis of SS by activating self-reactive B cells, and we also provide preliminary evidence for the diagnosis of SS by detecting BAFF-R on labial salivary glands.