Circulating and Synovial Pentraxin-3 (PTX3) Expression Levels Correlate With Rheumatoid Arthritis Severity and Tissue Infiltration Independently of Conventional Treatments Response.
Circulating and Synovial Pentraxin-3 (PTX3) Expression Levels Correlate With Rheumatoid Arthritis Severity and Tissue Infiltration Independently of Conventional Treatments Response.
复制标题
DOI：
10.3389/fimmu.2021.686795
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Pitzalis C
中科院分区：
文献类型：
--
作者：
Boutet MA;Nerviani A;Lliso-Ribera G;Leone R;Sironi M;Hands R;Rivellese F;Del Prete A;Goldmann K;Lewis MJ;Mantovani A;Bottazzi B;Pitzalis C
在一组早期治疗naïve患者中，确定PTX3系统和滑膜水平与类风湿关节炎（RA）临床特征之间的关系，并探讨PTX3表达在预测常规合成（cs）抗病抗风湿药物（DMARDs）治疗反应中的相关性。分析了来自早期naïve RA患者的119份基线血清样本、cs-DMARDs治疗开始6个月后获得的95份配对样本和43名健康供者的PTX3表达。分别对79和58个滑膜样本亚群进行PTX3的rna测序分析和免疫组化，以评估PTX3基因和蛋白的表达。免疫荧光染色表征滑膜内表达PTX3的细胞。与健康供者相比，早期RA患者的循环PTX3水平显著高于健康供者，并且与基线时的疾病活动度和12个月时的结构损伤程度相关。在开始cs- dmard治疗6个月后，无论患者的反应状态如何，仍可在患者血清中检测到与基线值成正比的高水平PTX3。RNA-seq分析证实，滑膜转录物PTX3水平与疾病活动性以及炎症、组织重塑和骨破坏介质的存在相关。PTX3在滑膜中的表达与免疫细胞浸润程度、异位淋巴样结构的存在和自身抗体的血清阳性密切相关。因此，PTX3被发现在许多滑膜细胞类型中表达，如浆细胞、成纤维细胞、血管和淋巴内皮细胞、巨噬细胞和中性粒细胞。虽然ptx3阳性滑膜细胞的百分比在治疗后6个月由于整体细胞减少而显著减少，但在cs-DMARDs应答者和无应答者中相似。本研究表明，在疾病早期和治疗调整之前，循环PTX3水平是RA活动的可靠标志，并预测12个月时高度的结构损伤。在关节中，PTX3与免疫细胞浸润和异位淋巴样结构的存在有关。高水平的滑膜和外周血PTX3与风湿性关节炎的慢性炎症特征有关。还需要进一步的研究来确定其中的机理联系。
To determine the relationship between PTX3 systemic and synovial levels and the clinical features of rheumatoid arthritis (RA) in a cohort of early, treatment naïve patients and to explore the relevance of PTX3 expression in predicting response to conventional-synthetic (cs) Disease-Modifying-Anti-Rheumatic-Drugs (DMARDs) treatment. PTX3 expression was analyzed in 119 baseline serum samples from early naïve RA patients, 95 paired samples obtained 6-months following the initiation of cs-DMARDs treatment and 43 healthy donors. RNA-sequencing analysis and immunohistochemistry for PTX3 were performed on a subpopulation of 79 and 58 synovial samples, respectively, to assess PTX3 gene and protein expression. Immunofluorescence staining was performed to characterize PTX3 expressing cells within the synovium. Circulating levels of PTX3 were significantly higher in early RA compared to healthy donors and correlated with disease activity at baseline and with the degree of structural damages at 12-months. Six-months after commencing cs-DMARDs, a high level of PTX3, proportional to the baseline value, was still detectable in the serum of patients, regardless of their response status. RNA-seq analysis confirmed that synovial transcript levels of PTX3 correlated with disease activity and the presence of mediators of inflammation, tissue remodeling and bone destruction at baseline. PTX3 expression in the synovium was strongly linked to the degree of immune cell infiltration, the presence of ectopic lymphoid structures and seropositivity for autoantibodies. Accordingly, PTX3 was found to be expressed by numerous synovial cell types such as plasma cells, fibroblasts, vascular and lymphatic endothelial cells, macrophages, and neutrophils. The percentage of PTX3-positive synovial cells, although significantly reduced at 6-months post-treatment as a result of global decreased cellularity, was similar in cs-DMARDs responders and non-responders. This study demonstrates that, early in the disease and prior to treatment modification, the level of circulating PTX3 is a reliable marker of RA activity and predicts a high degree of structural damages at 12-months. In the joint, PTX3 associates with immune cell infiltration and the presence of ectopic lymphoid structures. High synovial and peripheral blood levels of PTX3 are associated with chronic inflammation characteristic of RA. Additional studies to determine the mechanistic link are required.
登录
查看更多内容
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
DOI：
10.1084/jem.20150282
发表时间：
2016-09-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chorny A;Casas-Recasens S;Sintes J;Shan M;Polentarutti N;García-Escudero R;Walland AC;Yeiser JR;Cassis L;Carrillo J;Puga I;Cunha C;Bastos H;Rodrigues F;Lacerda JF;Morais A;Dieguez-Gonzalez R;Heeger PS;Salvatori G;Carvalho A;Garcia-Sastre A;Blander JM;Mantovani A;Garlanda C;Cerutti A
通讯作者：
Cerutti A
影响因子：
4.7
作者：
Hollan, Ivana;Bottazzi, Barbara;Meroni, Pier Luigi
通讯作者：
Meroni, Pier Luigi
影响因子：
3.7
作者：
Deyab G;Hokstad I;Whist JE;Småstuen MC;Agewall S;Lyberg T;Bottazzi B;Meroni PL;Leone R;Hjeltnes G;Hollan I
通讯作者：
Hollan I
影响因子：
3.7
作者：
Bottazzi B;Santini L;Savino S;Giuliani MM;Dueñas Díez AI;Mancuso G;Beninati C;Sironi M;Valentino S;Deban L;Garlanda C;Teti G;Pizza M;Rappuoli R;Mantovani A
通讯作者：
Mantovani A