小狗阅读会员会员
有解析的医学SCI阅读工具

扫码登录小狗阅读

阅读SCI医学文献

Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients.

比利时系统性硬化症患者大队列中原发性胆汁性胆管炎相关血清学特征的评价。

  • 影响因子:2.44
  • DOI:10.1515/cclm-2019-0655
  • 作者列表:"Florin L","Rubben K","Vanhaecke A","Devreese K","De Keyser F","Smith V","Bonroy C
  • 发表时间:2020-02-25
Abstract

:Background Systemic sclerosis (SSc) and primary biliary cholangitis (PBC) are autoimmune diseases that may occur concomitantly and are both strongly associated with disease-specific autoantibodies. This study investigated the prevalence and fine specificity of PBC-specific serology (PBC-Ab) and associations with the SSc-subtypes and SSc-specific antibodies as well as the association with cholestatic liver enzymes. Furthermore, three different techniques for the detection of PBC-Ab were compared. Methods Serum of 184 Belgian SSc patients with a known SSc-antibody profile, was analyzed for PBC-Ab (antimitochondrial antibodies [AMA], anti-Gp210, anti-Sp100 and anti-PML) using indirect immunofluorescence (IIF) analysis on human epithelioma-2000 (HEp-2000) cells (ANA-IIF, Immunoconcepts) and liver-kidney-stomach tissue sections (IIF-LKS) (Menarini), and a line immunoblot (LB) (EuroImmun). Alkaline phosphatase/γ-glutamyl transferase (ALP/GGT) were evaluated at time of first sampling (t0) and after 3 years of follow-up (t3). Results PBC-Ab were present in 13% of patients and significantly correlated with centromere antibodies (anti-CENP-B), but not correlated with the limited cutaneous SSc subgroup (lcSSc). The most frequent reactivities were AMA (11%, with 9% AMA-M2) and Sp-100 antibodies (5%), showing a major overlap. There was no relevant association between the presence of PBC-Ab and ALP or GGT elevation at t0 nor at t3. Detection of AMA with IIF-LKS is comparable to LB. ANA-IIF screening was less sensitive compared to LB. Conclusions A wide range of PBC-Ab is detectable in SSc in the absence of cholestatic liver enzyme elevations, even after 3 years of follow-up. However, as these antibodies may precede PBC-disease up to 10 years further prospective follow-up of our cohort will be necessary.

摘要

背景: 系统性硬化症 (SSc) 和原发性胆汁性胆管炎 (PBC) 是可能同时发生的自身免疫性疾病,两者均与疾病特异性自身抗体密切相关。本研究调查了 PBC 特异性血清学 (PBC-Ab) 的患病率和精细特异性,以及与 SSc 亚型和 SSc 特异性抗体的相关性,以及与胆汁淤积性肝酶的相关性。此外,对三种不同的检测 PBC-Ab 的技术进行了比较。方法对 184 例已知 SSc 抗体谱的比利时 SSc 患者的血清进行 PBC-Ab (抗线粒体抗体 [AMA] 、 anti-Gp210 、 anti-Sp100 和抗 PML) 分析。使用间接免疫荧光 (IIF) 分析人上皮瘤-2000 (HEp-2000) 细胞 (ANA-IIF,免疫概念) 和肝-肾-胃组织切片 (IIF-LKS) (美纳里尼),和线免疫印迹 (LB) (EuroImmun)。在首次取样时 (t0) 和随访 3 年后 (t3) 评估碱性磷酸酶/γ-谷氨酰转移酶 (ALP/GGT)。结果 13% 的患者存在 PBC-Ab,与着丝粒抗体 (抗 CENP-B) 显著相关,但与局限性皮肤 SSc 亚组 (lcSSc) 无关。最常见的反应是 AMA (11%,9% AMA-M2) 和 Sp-100 抗体 (5%),显示出主要的重叠。在 t0 和 t3 时,PBC-Ab 的存在与 ALP 或 GGT 升高之间没有相关关联。用 IIF-LKS 检测 AMA 与 LB 相当。与 LB 相比,ANA-IIF 筛查敏感性较低。结论在没有胆汁淤积性肝酶升高的情况下,在 SSc 中可检测到广泛的 PBC-Ab,即使在 3 年的随访后也是如此。然而,由于这些抗体可能先于 PBC-疾病长达 10 年,我们队列的进一步前瞻性随访将是必要的。

下载该文献
小狗阅读

帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。

相关文献
影响因子:6.87
发表时间:2020-01-10
DOI:10.1002/hep.31110
作者列表:["Goeppert B","Folseraas T","Roessler S","Kloor M","Volckmar AL","Endris V","Buchhalter I","Stenzinger A","Grzyb K","Grimsrud MM","Gornicka B","von Seth E","Reynolds GM","Franke A","Gotthardt DN","Mehrabi A","Cheung A","Verheij J","Arola J","Mäkisalo H","Eide TJ","Weidemann S","Cheville JC","Mazza G","Hirschfield GM","Ponsioen CY","Bergquist A","Milkiewicz P","Lazaridis KN","Schramm C","Manns MP","Färkkilä M","Vogel A","International PSC study group.","Boberg KM","Schirmacher P","Karlsen TH"]

METHODS:BACKGROUND & AIMS:Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) exceeds 20% and BTC is currently the leading cause of death in PSC patients. To open new avenues for management, we aimed to delineate novel and clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). APPROACH & RESULTS:We analysed formalin fixed, paraffin embedded tumor tissue from 186 PSC-BTC patients from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations and copy number variations, along with histomorphological and immunohistochemical characterization. Irrespective of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, e.g. TP53 (35.5%), KRAS (28.0%), CDKN2A (14.5%), and SMAD4 (11.3%), as well as potentially druggable mutations (e.g. HER2/ERBB2). We found a high frequency of non-typical/non-ductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%) CONCLUSION: Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC show a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC.

翻译标题与摘要 下载文献
影响因子:3.72
发表时间:2020-01-16
DOI:10.1093/ibd/izz325
作者列表:["Peverelle M","Paleri S","Hughes J","De Cruz P","Gow PJ"]

METHODS:BACKGROUND:The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS:One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score-Crohn's Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD. RESULTS:Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81-27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55-22.74; P < 0.001). CONCLUSIONS:Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC.

翻译标题与摘要 下载文献
影响因子:6.87
发表时间:2020-01-23
DOI:10.1002/hep.31140
作者列表:["Kunzmann LK","Schoknecht T","Poch T","Henze L","Stein S","Kriz M","Grewe I","Preti M","Hartl J","Pannicke N","Peiseler M","Sebode M","Zenouzi R","Horvatits T","Böttcher M","Petersen BS","Weiler-Normann C","Hess LU","Elise Ahrenstorf A","Lunemann S","Martrus G","Fischer L","Li J","Carambia A","Kluwe J","Huber S","Lohse AW","Franke A","Herkel J","Schramm C","Schwinge D"]

METHODS::T cells from patients with primary sclerosing cholangitis (PSC) show a prominent IL-17 response upon stimulation with bacteria or fungi, yet the reasons for this dominant TH17 response in PSC are not clear. Here, we analyzed the potential role of monocytes in microbial recognition and in skewing the T cell response towards Th17. Monocytes and T cells from blood and livers of PSC patients and controls were analyzed ex vivo and in vitro using trans-well experiments with cholangiocytes. Cytokine production was measured using flow cytometry, ELISA, RNA in situ hybridization and quantitative real time PCR. Genetic polymorphisms were obtained from Immunochip analysis. Following ex vivo stimulation with PMA/Ionomycin, PSC patients showed significantly increased numbers of IL-17A-producing peripheral blood CD4+ T cells compared to PBC patients and healthy controls, indicating increased Th17 differentiation in vivo. Upon stimulation with microbes, monocytes from PSC patients produced significantly more IL-1β and IL-6, cytokines known to drive Th17 cell differentiation. Moreover, microbe-activated monocytes induced the secretion of Th17 and monocyte-recruiting chemokines CCL-20 and CCL-2 in human primary cholangiocytes. In livers of patients with PSC cirrhosis, CD14hi CD16int and CD14lo CD16hi monocytes/macrophages were increased compared to alcoholic cirrhosis and monocytes were found to be located around bile ducts. Conclusion: PSC patients show increased Th17 differentiation already in vivo. Microbe-stimulated monocytes drive Th17 differentiation in vitro and induce cholangiocytes to produce chemokines mediating recruitment of Th17 cells and more monocytes into portal tracts. Taken together, these results point to a pathogenic role of monocytes in patients with PSC.

翻译标题与摘要 下载文献
方向

复制标题
发送后即可在该邮箱或我的下载查看该文献
发送
该文献默认存储到我的下载

科研福利

报名咨询

建议反馈
问题标题:
联系方式:
电子邮件:
您的需求: