原发性干燥综合征患者及其一级亲属外周血记忆性B细胞、B细胞激活因子及与临床指标的相关性Correlation of Memory B Cell and B Cell Activation Factor with Clinical Indicators in Primary Sjgren's Syndrome Patients and Their First-degree Relatives
王琳;张文;李梦涛;赵岩;
WANG Lin,ZHANG Wen,LI Meng-tao,ZHAO Yan Department of Rheumatology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100032,China
摘要(Abstract):
目的评价干燥综合征患者及一级亲属记忆性B细胞(CD19+CD27+B细胞)及B细胞激活因子(Bcell activation factor,BAFF)的外周表达及其与临床指标的相关性。方法以北京协和医院确诊的原发性干燥综合征(primary Sjgren's syndrome,pSS)患者41例、患者一级亲属7名及正常健康献血者27名的外周血为标本,用流式细胞仪分析记忆性B细胞,用ELISA法检测血浆B细胞激活因子(BAFF)水平,结合患者临床资料进行分析。结果原发性干燥综合征患者记忆性B细胞数目较正常人显著升高(11.10%±5.10%vs.9.24%±6.99%,P=0.0002),BAFF水平亦较正常人显著升高[(1.18±0.72)ng/mlvs.(0.43±0.19)ng/ml,P=0.0005];患者与其一级亲属的记忆性B细胞数目无显著性差异(16.26%±8.30%vs.8.75%±3.82%,P=0.088),患者的BAFF水平与其一级亲属比较显著升高[(1.29±0.46)ng/mlvs.(0.56±0.11)ng/ml,P=0.015]。结合临床资料分析,发现记忆性B细胞与5-min未刺激唾液量呈正相关(r=0.345,P=0.027),与眼科角结膜评分呈负相关(r=-0.321,P=0.041),与血清IgM、IgA、IgG、补体C3、补体C4无相关关系(P>0.05)。BAFF与血清IgM、IgA、IgG、补体C3、补体C4、口腔科灶性指数、眼科角结膜评分无相关关系(P>0.05)。结论记忆性B细胞在患者及其一级亲属高表达,与临床客观指标评价相反,提示记忆性B细胞在原发性干燥综合征疾病发生发展过程中可能存在从外周向腺体组织的迁移;患者BAFF水平明显高于正常人及其一级亲属,与临床指标不相关,表明BAFF可能参与原发性干燥综合征发生后的一系列反应而并非直接引起疾病,并且其水平尚不足以反映疾病的严重程度。
Objectives To investigate the expression of CD19+CD27+ (memory B cell) and B cell activation factor(BAFF),in the peripheral blood of patients with primary Sjgren's syndrome (pSS) and their relatives and to analyze the correlations of the cells with clinical indicator. Methods Peripheral venous bloodsamples were collected from 41 newly diagnosed pSS patients[females,age 48.7±9.1 years,anti-SSA/SSB (+) 73.2%] from Sjgren's International Collaborative Clinical Alliance(SICCA) and Peking Union Medical College Hospital(PUMCH),and 27 healthy controls (females,age 47.0±3.8 years) and 7 first-degree relatives of the patients (females,age 50.1±5.0 years). The levels of memory B cells in the peripheral blood were measured by flow-cytometric. The level of BAFF in serum was determined with enzyme-linked immunosorbent assay (ELISA). Clinical indicators including IgG,IgA,IgM,C3,C4,Focus score,5-min salivary rate,ocular score,Schirmer test results were tested simultaneously. Results The level of memory B cell in the blood of pSS patients was 11.10%±5.10%,which was significantly higher than that of the healthy controls 9.24%±6.99% (P=0.0002),but was not significant differences between pSS patients and their first-degree relatives (P>0.05). BAFF in pSS was 1.18±0.72 ng/ml,which was significantly higher than that of the healthy controls (0.43±0.19 ng/ml) (P=0.0005) and than that of their first-degree relatives (0.56±0.11 ng/ml) (P=0.015). CD27+ B cell were positively correlated with 5-min salivary rate (r=0.345,P=0.027),negatively correlated with ocular score (r=-0.321,P=0.041) ; however,it was not correlated with IgG,IgA,IgM,C3,C4,focus score,and Schirmer test results. BAFF was not correlated with IgG,IgA,IgM,C3,C4,focus score,5-min salivary rate,ocular score,and Schirmer test (P>0.05). Conclusions The memory B cell is highly expressed in pSS patients and their first-degree relatives and is negatively correlated with clinical indicators,suggesting that memory B cell may migrate from peripheral tissues to the gland tissues during the pathogenesis of pSS. BAFF level is remarkably higher in pSS patients than in their first-degree relatives and in healthy controls,suggesting that BAFF may be involved in the development of pSS but is not parallel with the severity of this disease.
关键词(KeyWords):
原发性干燥综合征;记忆性B细胞;B细胞激活因子;流式细胞仪;临床指标
primary Sjgren's syndrome; memory B cell; B cell activation factor; flowcytomentry; clinical indicator
基金项目(Foundation): “十一五”国家科技支撑项目(2008BAI59B03)
作者(Author):
王琳;张文;李梦涛;赵岩;
WANG Lin,ZHANG Wen,LI Meng-tao,ZHAO Yan Department of Rheumatology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100032,China
Email:
DOI:
参考文献(References):
- [1]Hansen A,Odendahl M,Reiter K.Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sj gren s syndrome[J].Arthritis Rheum,2002,46:2160-2171.
- [2]Hansen A,Gosemann M,Pruss A.Abnormalities in periph-eral B cell memory of patients with primary Sj gren s syn-drome[J].Arthritis Rheum,2004,50:1897-1908.
- [3]Hansen A,Lipsky PE,D rner T.B cells in Sj gren s syn-drome:indications for disturbed selection and differentiation in ectopic lymphoid tissue[J].Arthritis Res Ther,2007,9:218.
- [4]Lund FE.Cytokine-producing B lymphocytes—key regula-tors of immunity[J].Curr Opin Immunol,2008,20:332-338.
- [5]Becker-Merok A,Nikolaisen C,Nossent HC.B-lymphocyte activating factor in systemic lupus erythematosus and rheu-matoid arthritis in relation to autoantibody levels,disease measures and time[J].Lupus,2006,15:570-576.
- [6]Morimoto S,Nakano S,Watanabe T.Expression of B-cell activating factorof the tumournecrosis factorfamily(BAFF)in Tcells in active systemic lupus erythematosus:the role ofBAFF in T cell-dependent B cell pathogenic autoantibody production[J].Rheumatology,2007,46:1083-1086.
- [7]Mariette X,Roux S,Zhang J.The level of BLyS(BAFF)correlates with the titre of autoantibodies in human Sj gren s syndrome[J].Ann Rheum Dis,2003,62:168-171.
- [8]Atsushi M,Bhan AK.A Case for Regulatory B Cells[J].J Immunol,2006,176:705-710.
- [9]Bouaziz JD,Yanaba K,Tedder TF.Regulatory B cells as inhibitors of immune responses and inflammation[J].Im-munol Rev,2008,224:201-214.
- [10]蔡丽敏,陈志强.B细胞活化因子与干燥综合征[J].国际皮肤性病学杂志,2007,33:95-97.
- [11]Hansen A,Daridon C,D rner T.What do we know about memory B cells in primary Sj gren s syndrome?[J].Auto-immun Rev,2010,9:600-603.
- [12]Roguedas AM,Pers JO,Lemasson G,et al.Memory B-cell aggregates in skin biopsy are diagnostic for primary Sj gren s syndrome[J].J Autoimmun,in Press.
- [13]Darce JR,ArendtBK,Chang SK.Effects of BAFFon human memory B cell differentiation into Ig-secreting cells[J].J Immunol,2007,178:5612-5622.
- [14]Mariete X,Roux S,Zhang J,et al.The level of BLyS(BAFF)correlates with the titre of autoantibodies in human Sj gren s syndrome[J].Ann Rheum Dis,2003,62:168,171.
- [15]Varin MM,Pottier LL,Youinou P.B-cell tolerance break-down in Sj gren s syndrome:focus on BAFF[J].Autoim-mun Rev,2010,9:604-608.
- 原发性干燥综合征
- 记忆性B细胞
- B细胞激活因子
- 流式细胞仪
- 临床指标
primary Sjgren's syndrome - memory B cell
- B cell activation factor
- flowcytomentry
- clinical indicator
- 王琳
- 张文
- 李梦涛
- 赵岩
WANG Lin- ZHANG Wen
- LI Meng-tao
- ZHAO Yan Department of Rheumatology
- Peking Union Medical College Hospital
- Chinese Academy of Medical Sciences & Peking Union Medical College
- Beijing 100032
- China
- 王琳
- 张文
- 李梦涛
- 赵岩
WANG Lin- ZHANG Wen
- LI Meng-tao
- ZHAO Yan Department of Rheumatology
- Peking Union Medical College Hospital
- Chinese Academy of Medical Sciences & Peking Union Medical College
- Beijing 100032
- China