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人类白细胞抗原 G 在强直性脊柱炎中的作用及其在肿瘤坏死因子-α 阻滞剂治疗后的反应。

Human leukocyte antigen-G in ankylosing spondylitis and the response after tumour necrosis factor-alpha blocker therapy.

机构信息

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

出版信息

Rheumatology (Oxford). 2010 Feb;49(2):264-70. doi: 10.1093/rheumatology/kep360. Epub 2009 Dec 11.

Abstract

OBJECTIVE

To investigate the role of HLA-G in AS.

METHODS

Serum levels of soluble HLA-G (sHLA-G) were measured in 80 AS patients and 30 healthy controls. The expression of HLA-G on the peripheral blood mononuclear cell (PBMC) surface was investigated in the same 80 AS patients and 40 healthy controls by flow cytometry. The response of HLA-G after 3 months of TNF-alpha blocker therapy (adalimumab) was evaluated in 14 AS patients. We evaluated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), physical mobility, ESR and CRP levels.

RESULTS

Serum levels of sHLA-G were significantly lower in 80 AS patients than 30 healthy controls [mean (s.d.) 22.47 (26.8) vs 34.78 (32.01) U/ml, P = 0.028], and correlated significantly with modified Schober index (r = 0.326; P = 0.009), chest expansion (r = 0.319; P = 0.011), lateral lumbar flexion (r = 0.377; P = 0.002), cervical rotation (r = 0.396; P = 0.004), whereas inversely correlated with fingertip-to-floor distance (r = -0.282; P = 0.026) and tragus-to-wall distance (r = -0.270; P = 0.031). The expression of HLA-G on PBMCs was significantly higher in 80 AS patients than 40 healthy controls [mean (s.d.) 18.5 (6.10)% vs 15.41 (4.84)%; P = 0.012], and correlated significantly with ESR (r = 0.421; P < 0.001) and CRP (r = 0.419; P < 0.001). The expression of HLA-G on PMBCs decreased significantly after 3 months of adalimumab therapy [third month vs baseline, 13.46 (5.38)% vs 19.87 (7.31)%; P = 0.016].

CONCLUSIONS

Lower serum levels of sHLA-G contribute to susceptibility to AS, and predispose to poor spinal mobility. The expression of HLA-G on PMBCs is up-regulated in AS, correlates with acute phase reactants and decreases after TNF-alpha blocker therapy, suggesting an index of disease activity.

摘要

目的

探讨 HLA-G 在 AS 中的作用。

方法

检测 80 例 AS 患者和 30 例健康对照者血清可溶性 HLA-G(sHLA-G)水平,采用流式细胞术检测 80 例 AS 患者和 40 例健康对照者外周血单个核细胞(PBMC)表面 HLA-G 的表达。对 14 例 AS 患者进行 3 个月 TNF-α 阻滞剂(阿达木单抗)治疗后的 HLA-G 反应进行评估。评估 Bath 强直性脊柱炎疾病活动指数(BASDAI)、Bath 强直性脊柱炎功能指数(BASFI)、Bath 强直性脊柱炎患者总体评分(BAS-G)、身体活动度、ESR 和 CRP 水平。

结果

80 例 AS 患者血清 sHLA-G 水平明显低于 30 例健康对照组[均值(标准差):22.47(26.8)比 34.78(32.01)U/ml,P=0.028],与改良 Schober 指数(r=0.326;P=0.009)、胸廓扩张度(r=0.319;P=0.011)、腰椎侧屈度(r=0.377;P=0.002)、颈椎旋转度(r=0.396;P=0.004)呈正相关,与指尖距地面距离(r=-0.282;P=0.026)和耳垂距墙距离(r=-0.270;P=0.031)呈负相关。80 例 AS 患者 PBMC 上 HLA-G 的表达明显高于 40 例健康对照组[均值(标准差):18.5(6.10)%比 15.41(4.84)%,P=0.012],与 ESR(r=0.421;P<0.001)和 CRP(r=0.419;P<0.001)呈正相关。阿达木单抗治疗 3 个月后,PMBCs 上 HLA-G 的表达明显下降[第 3 个月与基线相比,13.46(5.38)%比 19.87(7.31)%,P=0.016]。

结论

血清 sHLA-G 水平降低与 AS 的易感性有关,并导致脊柱活动度下降。AS 患者 PMBCs 上 HLA-G 的表达上调,与急性期反应物相关,TNF-α 阻滞剂治疗后降低,提示疾病活动指数。

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