目的评价白细胞介素(IL)-1基因多态性与强直性脊柱炎(AS)发病的相关性。方法利用荟萃分析的方法综合已发表的相关文献中的研究数据。检索 Pubmed、EMBASE、Cochrane 图书馆和中国生物医学文献数据库(CBM),收集所有 AS 相关的病例对照研究。纳入标准:纳入文献内容涉及白细胞介素(IL)-1基因多态性与 AS 的病例对照研究;AS 诊断按照1984年修订的纽约诊断标准,由风湿专科医生作出诊断;原始数据提供等位基因频率和/或基因型频率;被研究位点在对照人群中符合 Hardy-Weinberg 平衡。剔除标准:不符合纳入标准,重复报道及家系研究。结果 (1)经全面检索纳入6篇文献,共9个研究人群。总体数据合并统计呈明显异质性。分别按高加索人种和蒙古人种进行分层后亚组内各研究间具有同质性。(2)荟萃分析显示,IL-1RN 第2内含子中的数目可变串联重复(VNTR)多态性等位基因2在高加索人种 AS 患者中频率增高,该等位基因 OR=1.52(95%CI=1.26～1.84,P<0.01),相应基因型 OR=1.33(95%CI=1.04～1.70,P<0.05);但是,该等位基因在蒙古人种 AS 患者中的频率比对照组低,等位基因 OR=0.55(95%CI=0.38～0.81,P<0.01),基因型 OR=0.51(95%CI=0.34～0.77,P<0.01)。(3)IL-1A-889 C>T(rs1800587)的次要等位基因 T 在高加索人种 AS 患者中频率增高,OR=1.36(95%CI=1.12～1.66,P<0.01),相应基因型 C/T+T/T 的 OR=1.56(95%CI=1.20～2.03,P<0.01)。但在蒙古人种人群中差异无统计学意义。(4)在高加索人种人群中,IL-1F8的 SNP rs1900287的次要等位基因 G 在 AS 患者中频率增加,OR=1.22(95%CI=1.04～1.44,P<0.05)。结论作为一种复杂性状疾病,AS 发病的遗传易感因素可能与 IL-1基因多态性相关,相关的多态性位点有 IL-1RN 第2内含子86 bpVNTR、IL-1A-889C>T(rs1800587)和 IL-1F8的 SNP rs1900287。IL-1基因多态性与疾病的关联有明显的人种差异。
Background The role of B-cell remains an enigma in the pathogenesis of ankylosing spondylitis （AS）. This study aimed to investigate the distributions of B-cells and subsets in peripheral blood of AS patients and observe their changes in etanercept-treated AS patents. Methods We detected the proportions of CD19^＋ B-cell, naive B-cell （CD19^＋CD27）, memory B-cell （CD19^＋CD27dim） and plasmablast （CD19^＋CD27high） in peripheral blood of 66 patients with AS （39 at active stage, 27 at stable stage; 35 patients with peripheral joint involvement, 31 patients with axial involvement alone）, 30 patients with rheumatoid arthritis （RA） and 30 healthy volunteers using flow cytometry. And then we observed the changes of the above indexes of 39 active AS patients treated with etanercept in a randomized, double-blind, placebo-controlled trial. Results （1） Percentages of CD19^＋ B-cells in active or peripheral joint involvement AS patients increased more obviously than those in stable or axial involvement alone AS patients （both P=0.001）, and percentage of CD19^＋CD27high B-cells in AS patients with peripheral joint involvement was significantly higher than that in cases with axial involvement alone or healthy volunteers （P=0.005 and 0.006, respectively）; （2） The percentage of CD19~ B-cells in AS patients was positively correlated with Bath Ankylosing Spondylitis Disease Activity Index （BASDAI） scores, Patient＇s Global Assessment （PGA） scores, total back pain scores and nocturnal back pain scores （r=0.270, 0.255, 0.251 and 0.266, P=-0.029, 0.039, 0.042 and 0.031, respectively）; （3） At week 6 and week 12, there were no statistical differences of the percentages of B-cells and subsets between etanercept group and placebo group of AS patients （P 〉0.05）; the percentage of CD19^＋ B-cells in etanercept group was higher than that in healthy volunteers at week 12 （t=3.320, P=0.003）. Conclusions Misbalance is present in B-cells and some subsets in peripheral bloo
LIN Qu GU Jie-ruo LI Tian-wang ZHANG Fu-cheng LIN Zhi-ming LIAO Ze-tao WEI Qiu-jing CAO Shuang-yan LI Li
