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

Cytokine and autoantibody profiling related to histopathological features in primary Sjogren's syndrome
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DOI:
10.1093/rheumatology/kep149
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发表时间:
2009-09-01
期刊:
影响因子:
5.5
通讯作者:
Brokstad, Karl A.
Brokstad, Karl A.
中科院分区:
医学1区
文献类型:
--
作者:
Reksten, Tove R.;Jonsson, Malin V.;Brokstad, Karl A.

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目标。目的探讨原发性血瘀证(PSS)患者外周血中细胞因子、自身抗体水平与组织病理学特征之间的关系。对141例符合美欧PSS共识分类标准的患者的小涎腺活检进行了重新检查,并根据病灶评分(FS)和生发中心(GC)状态进行分组;对血清样本进行自身抗体、趋化因子和细胞因子分析。在115例可用活检中,18例(16%)缺乏特征性局灶性单核细胞浸润[FS<1(FS-)],但患者Ro/SSA和/或La/SSB阳性。唾液腺异位GC形成(GC+)患者中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、干扰素-α和IL-4水平显著高于GC-患者(n=70)。此外,在比较各年龄组时,发现细胞因子水平略有不同。在PSS患者的小唾液腺中观察到的退行性变化可能代表着“烧毁”的炎症。在这些患者中发现的IL-4水平升高可能会影响在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亚单位IL-12p40滴度的升高可能表明GC+患者这些细胞的活性较高。在将SS患者分成不同的疾病阶段时,细胞因子水平的差异可能会被利用,因此可能会对治疗产生影响。
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)-1 alpha, MIP-1 beta, 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-1 beta 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.