دورية أكاديمية
Serologically assessed heat shock protein 47 is related to fibrosis stage in early compensated alcohol-related liver disease
| العنوان: | Serologically assessed heat shock protein 47 is related to fibrosis stage in early compensated alcohol-related liver disease |
|---|---|
| المؤلفون: | Lønsmann, Ida, Gudmann, Natasja Stæhr, Manon-Jensen, Tina, Thiele, Maja, Moreno, Ydalina Maria, Langholm, Lasse Løcke, Nielsen, Mette Juul, Detlefsen, Sönke, Karsdal, Morten Asser, Krag, Aleksander Ahm, Leeming, Diana Julie |
| المصدر: | Lønsmann , I , Gudmann , N S , Manon-Jensen , T , Thiele , M , Moreno , Y M , Langholm , L L , Nielsen , M J , Detlefsen , S , Karsdal , M A , Krag , A A & Leeming , D J 2022 , ' Serologically assessed heat shock protein 47 is related to fibrosis stage in early compensated alcohol-related liver disease ' , Clinical Biochemistry , vol. 104 , pp. 36-43 . https://doi.org/10.1016/j.clinbiochem.2021.12.008Test |
| سنة النشر: | 2022 |
| المجموعة: | University of Southern Denmark: Research Output / Syddansk Universitet |
| مصطلحات موضوعية: | Biomarker development, Biomarker validation, Collagen chaperone, Fibrosis assessment, Non-invasive biomarker, Cross-Sectional Studies, HSP47 Heat-Shock Proteins/metabolism, Humans, Fibrosis, Liver Cirrhosis, Collagen/metabolism |
| الوصف: | BACKGROUND AND AIMS: Heat shock protein (HSP)47 is a collagen-specific chaperone, essential for the correct formation of fibrillar procollagens. Collagen accumulation in the extracellular matrix (ECM) is a hallmark of fibrogenesis. The expression of HSP47 is proportional to the rate of collagen formation. Thus, HSP47 is a potential drug target for fibrotic diseases. We hypothesized that a C-terminal fragment of HSP47 (HSP47-C) could be quantified serologically and related to liver fibrosis stage. For this, a novel competitive enzyme-linked immunosorbent assay (ELISA) was developed. METHOD: An ELISA employing a monoclonal antibody targeting HSP47-C was developed and technically validated. The assay was evaluated in serum from a cross-sectional biopsy-controlled study of 281 patients with alcohol-related liver disease (ALD) and 50 gender, age and BMI matched healthy controls (HC). All liver biopsies from ALD patients were scored by one pathologist according to fibrosis stage (F0-4). RESULTS: The HSP47-C assay was technically robust and specific for the target sequence. HSP47-C was 39% higher in ALD patients (median 17.7 ng/mL, IQR 12.4-24.0 ng/mL) compared to HC (median 12.7 ng/mL, IQR 9.4-15.7 ng/mL, p<0.0001). In addition, HSP47-C was elevated in patients with severe fibrosis (F3-4, median 22.8 ng/mL, IQR 17.5-33.3 ng/mL) compared to none-to-moderate fibrosis (F0-2, median 16.5 ng/mL, IQR 11.8-22.5 ng/mL) with an AUROC of 0.72 (p<0.0001). HSP47-C also correlated with other liver disease parameters, albumin, bilirubin and aspartate transaminase. CONCLUSION: We developed a competitive ELISA for serological detection of HSP47-C. The study supports HSP47 as a potential marker of liver fibrosis in ALD. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://portal.findresearcher.sdu.dk/da/publications/5ac8c3df-73d1-4fff-8b0c-510c457140e8Test |
| DOI: | 10.1016/j.clinbiochem.2021.12.008 |
| الإتاحة: | https://doi.org/10.1016/j.clinbiochem.2021.12.008Test https://portal.findresearcher.sdu.dk/da/publications/5ac8c3df-73d1-4fff-8b0c-510c457140e8Test https://findresearcher.sdu.dk/ws/files/202901221/1_s2.0_S0009912021003386_main.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6754C61D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.clinbiochem.2021.12.008 |
|---|