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原发性干燥综合征中与组织病理学特征相关的细胞因子和自身抗体分析

Cytokine and autoantibody profiling related to histopathological features in primary Sjogren's syndrome.

作者信息

Reksten Tove R, Jonsson Malin V, Szyszko Ewa A, Brun Johan G, Jonsson Roland, Brokstad Karl A

机构信息

Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway.

出版信息

Rheumatology (Oxford). 2009 Sep;48(9):1102-6. doi: 10.1093/rheumatology/kep149. Epub 2009 Jul 2.

Abstract

OBJECTIVE

To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS).

METHODS

Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American-European consensus classification criteria for pSS were re-examined and grouped according to focus score (FS) and germinal centre (GC) status; serum samples were analysed for autoantibodies, chemokines and cytokines.

RESULTS

Of the 115 available biopsies, 18 (16%) lacked characteristic focal mononuclear cell infiltrates [FS < 1 (FS-)] but patients were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, eotaxin, IFN-alpha and IL-4 levels were significantly increased in the 27 (23%) patients with ectopic GC formation (GC+) in the salivary glands compared with the GC- patients (n = 70). In addition, minor differences in cytokine levels were found when comparing age groups.

CONCLUSION

Degenerative changes observed in the minor salivary glands of patients with pSS may represent 'burned out' inflammation. The elevated levels of IL-4 found in these patients may influence the reduced salivary flow observed in GC+ patients. Increased titres of Th17-associated cytokines, IL-17, IL-1beta and the IL-23 subunit IL-12p40, may indicate a higher activity of these cells in GC+ patients. Differences in cytokine levels may be utilized when sub-grouping the SS patients into disease phases and may consequently have implications for treatment.

摘要

目的

研究原发性干燥综合征(pSS)患者亚组中循环细胞因子和自身抗体水平与组织病理学特征之间的潜在相关性。

方法

对141例符合pSS欧美共识分类标准的患者队列的小唾液腺活检标本进行重新检查,并根据灶性评分(FS)和生发中心(GC)状态进行分组;分析血清样本中的自身抗体、趋化因子和细胞因子。

结果

在115份可用的活检标本中,18份(16%)缺乏特征性的局灶性单核细胞浸润[FS<1(FS-)],但患者的Ro/SSA和/或La/SSB呈阳性。与GC-患者(n=70)相比,唾液腺中形成异位GC(GC+)的27例(23%)患者的IL-17、IL-1RA、IL-15、巨噬细胞炎性蛋白(MIP)-1α、MIP-1β、嗜酸性粒细胞趋化因子、IFN-α和IL-4水平显著升高。此外,比较年龄组时发现细胞因子水平存在微小差异。

结论

pSS患者小唾液腺中观察到的退行性改变可能代表“消退”的炎症。这些患者中IL-4水平升高可能影响GC+患者中观察到的唾液流量减少。Th17相关细胞因子IL-17、IL-1β和IL-23亚基IL-12p40的滴度升高可能表明这些细胞在GC+患者中具有更高的活性。细胞因子水平的差异可用于将SS患者亚组划分为疾病阶段,因此可能对治疗有影响。

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