Rose Thomas, Szelinski Franziska, Lisney Anna, Reiter Karin, Fleischer Sarah J, Burmester Gerd R, Radbruch Andreas, Hiepe Falk, Grützkau Andreas, Biesen Robert, Dörner Thomas
Department of Rheumatology and Clinical Immunology , Charité Universitätsmedizin Berlin , Berlin , Germany.
German Rheumatism Research Center (DRFZ) Berlin, a Leibniz Institute , Berlin , Germany.
RMD Open. 2016 Dec 30;2(2):e000292. doi: 10.1136/rmdopen-2016-000292. eCollection 2016.
To evaluate the interferon (IFN) biomarkers sialic acid binding Ig like lectin 1 (SIGLEC1, CD169) and IFN-γ-inducible protein-10 (IP-10) in patients with primary Sjögren's syndrome (pSS).
31 patients fulfilling the American-European criteria for pSS were included. Disease activity was obtained by EULAR Sjögren's syndrome disease activity index (ESSDAI). SIGLEC1 expression on monocytes was analysed using flow cytometry. IP-10 concentrations were determined using Bioplex human Cytokine 27-plex kit. Spearman rank test (SRT) was used for correlation analysis and Mann-Whitney U (MWU) to test for differences between glandular and extraglandular manifestations.
An activated IFN system was detected by an upregulation of SIGLEC1 expression in 64.5% and by elevated serum level of IP-10 in 78.9% of our patients with pSS. In a subsequent analysis SIGLEC1 expression was found to be upregulated more frequently in patients with extraglandular manifestations (16/16, 100%) compared to patients with exclusively glandular involvement (4/15, 27%). SIGLEC1 expression could significantly discriminate between these two disease subgroups (p=0.0001, MWU) with a positive predictive value (PPV) of 80% for extraglandular disease. Moreover, the expression correlated with disease activity (p=0.005, r=0.54, SRT). Serum IP-10 levels neither differed significantly between glandular and extraglandular disease nor correlated with ESSDAI.
Our results indicate that increased SIGLEC1 expression characterises patients with systemic involvement and high disease activity. Therefore, SIGLEC1 determination might be of value for subset definition, risk stratification and differential therapeutic considerations in pSS.
评估原发性干燥综合征(pSS)患者的干扰素(IFN)生物标志物唾液酸结合免疫球蛋白样凝集素1(SIGLEC1,CD169)和IFN-γ诱导蛋白10(IP-10)。
纳入31例符合美国-欧洲pSS标准的患者。通过欧洲抗风湿病联盟干燥综合征疾病活动指数(ESSDAI)评估疾病活动度。采用流式细胞术分析单核细胞上SIGLEC1的表达。使用Bioplex人细胞因子27项检测试剂盒测定IP-10浓度。采用Spearman秩和检验(SRT)进行相关性分析,采用Mann-Whitney U检验(MWU)检测腺体和腺外表现之间的差异。
在我们的pSS患者中,64.5%的患者通过SIGLEC1表达上调检测到激活的IFN系统,78.9%的患者通过血清IP-10水平升高检测到激活的IFN系统。在随后的分析中,发现与仅累及腺体的患者(4/15,27%)相比,腺外表现患者(16/16,100%)中SIGLEC1表达上调更为频繁。SIGLEC1表达可显著区分这两个疾病亚组(p = 0.0001,MWU),腺外疾病的阳性预测值(PPV)为80%。此外,该表达与疾病活动度相关(p = 0.005,r = 0.54,SRT)。血清IP-10水平在腺体疾病和腺外疾病之间无显著差异,也与ESSDAI无关。
我们的结果表明,SIGLEC1表达增加是系统性受累和高疾病活动度患者的特征。因此,测定SIGLEC1可能对pSS的亚组定义、风险分层和差异化治疗考虑具有价值。