Possible role of the HMGB1 and RAGE inflammatory pathway in primary sclerosing cholangitis - 27/02/22
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
| páginas | 9 |
| Iconografías | 3 |
| Vídeos | 0 |
| Otros | 0 |
Highlights |
• | This study aimed to assess the impact of proinflammatory HMGB1 and one of its receptors RAGE in PSC pathogenesis. |
• | Biliary HMGB1 was significantly elevated in PSC patients. |
• | A gain-of-function single nucleotide polymorphism (SNP) in RAGE was associated with development of dominant stenosis. |
• | PSC patients with the mutant allele of the RAGE SNP had significantly reduced transplantation-free survival. |
Abstract |
Background |
Activation of the receptor for advanced glycation end products (RAGE) and its ligand High Mobility Group Box Protein 1 (HMGB1), a nuclear protein with proinflammatory properties, has been implicated in several inflammatory disorders.
Objective |
To analyse the influence of RAGE and HMGB1 signalling in patients with primary sclerosing cholangitis (PSC).
Methods |
Levels of HMGB1 and bile acid in serum and bile samples of 69 PSC patients and 32 controls were measured. Additionally, 640 patients with PSC and other liver diseases were analysed for the gain-of-function RAGE G82S SNP by PCR. Laboratory and clinical parameters were retrieved by chart review.
Results |
ELISA analysis showed significantly higher biliary HMGB1 concentrations in PSC patients (n=69, median 124,1 ng/ml) than in the control group (n=32, median 6,85 ng/ml, p<0,001). Median serum HMGB1 (n=22, median 2,4 ng/ml) was significantly lower than median biliary HMGB1 of the concomitant bile samples (n=22, median 151 ng/ml, p =0,001). There was no correlation of biliary HMGB1 levels with laboratory parameters or clinical end points. Analysis of the gain-of-function G82SSNP RAGE SNP in PSC patients showed 8 patients with heterozygote mutant alleles (8/324, 2,5%). Patients carrying the mutation developed more often dominant strictures of the large bile ducts (100.0% vs. 61.3%; p=0.04) and had reduced transplantation-free survival in the mutant allele group (p<0.001).
Conclusions |
Biliary HMGB1 levels are elevated in PSC patients compared to controls and a gain-of-function SNP in RAGE is associated with development of dominant strictures and reduced survival in PSC patients.
El texto completo de este artículo está disponible en PDF.Keywords : Cholangitis, Sclerosing, HMGB1 protein, Receptors for advanced glycation end products, Biomarker
Abbreviations : PSC, RAGE, HMGB1, SNP, DAMP, TLR, SLE, ELISA, IQR, ALP, IBD, MRS, ERC
Esquema
Vol 46 - N° 2
Artículo 101791- février 2022 Regresar al número
Artículo precedente
- The efficacy and safety of 5-fluorouracil based adjuvant therapy in resected biliary tract cancer: A systematic review and meta-analysis
- Shaoming Song, Wenwen Yang, Hongwei Tian, Shiyi Gong, Caining Lei, Kun Lv, Tingting Lu, Qinghao Cheng, Kehu Yang, Tiankang Guo
- Targeting AGEs-RAGE pathway inhibits inflammation and presents neuroprotective effect against hepatic ischemia-reperfusion induced hippocampus damage
- Lingyun Ren, Hong Yan
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
La compra de artículos no está disponible en este momento.
¿Ya suscrito a @@106933@@ revista ?