Serum Cytokine Receptors in Ankylosing Spondylitis: Relationship to Inflammatory Markers and Endoplasmic Reticulum Aminopeptidase Polymorphisms
Serum Cytokine Receptors in Ankylosing Spondylitis: Relationship to Inflammatory Markers and Endoplasmic Reticulum Aminopeptidase Polymorphisms
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DOI：
10.3899/jrheum.100019
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发表时间：
2010-09-01
影响因子：
3.9
通讯作者：
Inman, Robert D.
中科院分区：
文献类型：
--
作者：
Haroon, Nigil;Tsui, Florence W. L.;Inman, Robert D.
Objective.内质网氨肽酶（ERAP）I与强直性脊柱炎（AS）相关，已知参与细胞因子受体白细胞介素1受体II（IL-IRII）、IL-6 R α和肿瘤坏死因子受体I（TNFRI）的剪切。我们研究了AS患者血清中这些细胞因子受体及其相应的细胞因子与炎症标志物和ERAP I和ERAP 2多态性的关系。采用ELISA法检测AS患者血清中TNF-α、IL-1、IL-6、sTNFRI、sIL-1 RII和sIL-6 R α的含量。对ERAP I基因中3个AS相关的非同义单核苷酸多态性[rs 27044（C/G）]进行基因分型。rs 10050860（C/T）和ERAP 2基因中的rs30187（C/T）1和I [rs 2549782（T/G）1]。比较不同基因型组间血清细胞因子和受体水平，并与炎症标志物和疾病活动度相关。入组了80例AS患者（21例女性），平均Bath强直性脊柱炎疾病活动指数（BASDAI）为5.3 ± 2.4。sTNERI与C-反应蛋白（CRP; R = 0.43，p < 0.001）和红细胞沉降率（ESR; R = 0.30，p = 0.01）显著相关，但与BASDAI无关。大多数患者血清细胞因子水平检测不到。不同ERAPHERAP 2基因多态性和单倍型患者血清细胞因子和可溶性受体水平无显著差异。同样，这些多态性与血清细胞因子水平和精氨酸-受体比值均无相关性。AS患者血清可溶性TNFRI水平与ESR、CRP相关。ERAP I和ERAP 2基因多态性与AS相关，但不影响AS患者血清细胞因子受体水平。（2010年7月1日首次发布; J Rheumol 2010;37：1907-10; doi：10.3899/jrheum.100019）
Objective. Endoplasmic reticulum aminopeptidase (ERAP)I is associated with ankylosing spondylitis (AS) and is known to be involved in the clipping of the cytokine receptors interleukin 1 receptor II (IL-IRII), IL-6R alpha, and tumor necrosis factor receptor I (TNFRI). We studied the relationship of these serum cytokine receptors and their corresponding cytokines to markers of inflammation and polymorphisms in ERAP I and ERAP2 in patients with AS.Methods. Sera from patients with AS were assayed for TNF-alpha, IL-1, IL-6, sTNFRI, sIL-1RII, and sIL-6R alpha by ELISA. Genotyping was performed for 3 AS-associated nonsynonymous single-nucleotide polymorphisms in the ERAP I gene [rs27044(C/G). rs10050860(C/T), and rs30187(C/T)1 and I in the ERAP2 gene [rs2549782(T/G)1]. The serum cytokine and receptor levels were compared between the different genotype groups and correlated to markers of inflammation and disease activity.Results. Eighty patients with AS (21 women) with a mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 5.3 +/- 2.4 were enrolled. There was a significant correlation of sTNERI with C-reactive protein (CRP; R = 0.43, p < 0.001) and erythrocyte sedimentation rate (ESR; R = 0.30, p = 0.01) but not with BASDAI. Serum cytokine levels were undetectable in the majority of patients. There was no significant difference in serum cytokines or the soluble receptors between patients with the different ERAPHERAP2 polymorphisms and their haplotypes. Similarly, there was no relationship of the polymorphisms with the serum cytokine levels nor the cytokine-receptor ratio.Conclusion. Soluble TNFRI levels correlate with ESR and CRP in AS. The ERAP I and ERAP2 polymorphisms associated with AS do not influence the serum cytokine receptor levels in patients with AS. (First Release July 1 2010; J Rheumatol 2010;37:1907-10; doi:10.3899/jrheum.100019)