FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3137162300> ?p ?o ?g. }

• W3137162300 endingPage "2251" @default.
• W3137162300 startingPage "2249" @default.
• W3137162300 abstract "See “Direct measurement of ATP7B peptides is highly effective in the diagnosis of Wilson disease,” by Collins CJ, Yi F, Dayuha R, et al, on page 2367. See “Direct measurement of ATP7B peptides is highly effective in the diagnosis of Wilson disease,” by Collins CJ, Yi F, Dayuha R, et al, on page 2367. The diagnosis of Wilson disease (WD) can be determined by a combination of parameters aiming to detect copper accumulation. In this article from Collins et al,1Collins C.J. Yi F. Dayuha R. et al.Direct measurement of ATP7B peptides is highly effective in the diagnosis of Wilson disease.Gastroenterology. 2021; 160: 2367-2382Abstract Full Text Full Text PDF Google Scholar a new approach to the diagnosis of WD is proposed. In current clinical practice, low ceruloplasmin levels are used as a minimal screening test, followed by Kayser–Fleischer ring assessment, 24-hour urine collection, liver biopsy for copper quantification, and brain magnetic resonance imaging for demonstration of copper-related changes in the basal ganglia. Although scoring systems can aid in the diagnostic process,2Ferenci P. Caca K. Loudianos G. et al.Diagnosis and phenotypic classification of Wilson disease.Liver Int. 2003; 23: 139-142Crossref PubMed Google Scholar the traditional laboratory tools lack sensitivity and specificity for WD. In particular, the major limitation of ceruloplasmin determination is that most clinical laboratories quantify the enzyme levels, but not its oxidase activity, with consequent determination of erroneous elevated levels owing to quantification of both ceruloplasmin and biologically inactive apoceruloplasmin.3Merle U. Eisenbach C. Weiss K.H. et al.Serum ceruloplasmin oxidase activity is a sensitive and highly specific diagnostic marker for Wilson's disease.J Hepatol. 2009; 51: 925-930Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Total serum copper is even less valuable as a screening test because it is influenced by ceruloplasmin level and its measurement methods. Genetic testing with ATP7B sequencing, whole-exome sequencing4Kluska A. Kulecka M. Litwin T. et al.Whole-exome sequencing identifies novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease phenotype.Liver Int. 2019; 39: 177-186Crossref PubMed Scopus (15) Google Scholar and whole-genome sequencing are considered confirmatory tests and their costs are becoming more approachable. Although ATP7B variants are associated with various degrees of functional impairment,5Huster D. Kühne A. Bhattacharjee A. et al.Diverse functional properties of Wilson disease ATP7B variants.Gastroenterology. 2012; 142: 947-956 e5Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar their clinical correlate is uncertain. Therefore, the major challenge is the lack of genotype–phenotype correlation,6Ferenci P. Stremmel W. Członkowska A. et al.Age and sex but not ATP7B genotype effectively influence the clinical phenotype of Wilson disease.Hepatology. 2019; 69: 1464-1476Crossref PubMed Scopus (50) Google Scholar with the additional concern that some gene variants may not be associated with clinical manifestation development. Other diagnostic options, including the radioactive copper incorporation test7Członkowska A. Rodo M. Wierzchowska-Ciok A. et al.Accuracy of the radioactive copper incorporation test in the diagnosis of Wilson disease.Liver Int. 2018; 38: 1860-1866Crossref PubMed Scopus (8) Google Scholar or the exchangeable copper,8Guillaud O. Brunet A.S. Mallet I. et al.Relative exchangeable copper: a valuable tool for the diagnosis of Wilson disease.Liver Int. 2018; 38: 350-357Crossref PubMed Scopus (23) Google Scholar are interesting but will likely offer several challenges in their access and execution outside selected academic centers. Therefore, although the diagnosis of WD is frequently achievable with available methods, many cases are trapped in a grey area of diagnostic uncertainty characterized by borderline ceruloplasmin levels, gene variants of unknown significance, and ambiguous clinical presentations. These borderline cases often overlap with common conditions, including fatty liver, autoimmune hepatitis, and movement disorders, and require refined clinical judgment and expertise for the final diagnosis. Striving for a gold standard and improved diagnostic assessment is important because WD is a treatable disease both in the acute and chronic phases and timely diagnosis can prevent, improve, and even resolve many of the clinical manifestations. Particularly concerning are the neuropsychiatric manifestations, which are debilitating and only responsive after years of anticopper treatment and physical therapy. In addition, new treatment options are on the horizon, including next-generation chelating agents9Weiss K.H. Askari F.K. Czlonkowska A. et al.Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study.Lancet Gastroenterol Hepatol. 2017; 2: 869-876Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar and gene therapy approaches.10Murillo O. Luqui D.M. Gazquez C. et al.Long-term metabolic correction of Wilson's disease in a murine model by gene therapy.J Hepatol. 2016; 64: 419-426Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Medical treatment is often limited by drug toxicity, and unsatisfactory improvement, especially of the severe neuropsychiatric symptoms, is frequent. Liver transplantation can be an effective treatment and is often inevitable in cases of acute liver failure, but chronic immunosuppression is not desirable.11Camarata M.A. Gottfried M. Rule J.A. et al.Outcomes of acute liver injury in adults due to Wilson's disease: is survival without transplant possible?.Liver Transpl. 2020; 26: 330-336Crossref PubMed Scopus (5) Google Scholar Therefore, when the phenotypic characterization of WD improves beyond the traditional definitions of prevalent hepatic and neuropsychiatric involvement,12Mordaunt C.E. Kieffer D.A. Shibata N.M. et al.Epigenomic signatures in liver and blood of Wilson disease patients include hypermethylation of liver-specific enhancers.Epigenetics Chromatin. 2019; 12: 10Crossref PubMed Scopus (16) Google Scholar,13Sarode G.V. Kim K. Kieffer D.A. et al.Metabolomics profiles of patients with Wilson disease reveal a distinct metabolic signature.Metabolomics. 2019; 15: 43Crossref PubMed Scopus (15) Google Scholar the goal will be to tailor and optimize medical treatment to the phenotype or predicted disease course. In this issue of Gastroenterology, Collins et al1Collins C.J. Yi F. Dayuha R. et al.Direct measurement of ATP7B peptides is highly effective in the diagnosis of Wilson disease.Gastroenterology. 2021; 160: 2367-2382Abstract Full Text Full Text PDF Google Scholar adopt a new approach to the diagnosis of WD based on the quantification of ATP7B protein concentration derived from measurement of 2 surrogate peptides in patient dried blood spot samples, as direct evidence of WD diagnosis. Two ATP7B peptides, ATP7B 887 and ATP7B 1056, were selected and measured with specific antibodies. The studied samples derived from pre-existing biorepositories originated from European, North American, and South Korean institutions providing samples from patients with WD (n = 216), obligate ATP7B variant carriers (n = 48), and healthy patients (n = 150). Patients with WD carried different ATP7B variants, mostly highly prevalent in the population of origin. The age range was 2 months to 73 years, which is important because it is now established that the diagnosis of WD should be considered at any age. The approach was first to identify the analytical and diagnostic performance of the peptides and identify the diagnostic cutoffs. A large proportion of the studied patients had available genetic test results and 92.1% of the patients with genetically confirmed WD had ≥1 of the peptides below the established minimal cutoffs. Among the 67 patients in whom genetic tests could not establish diagnosis of WD, 63 (94%) had their diagnosis clarified by low peptide levels. Of note, ≤16% of individuals heterozygous for WD had peptide levels below the cutoff, but could also have been WD cases carrying unknown variants. ATP7B 887 analysis demonstrated a sensitivity of 91.2% and specificity of 98.1%. In line with the challenges related to varied WD presentation, a small but sizable percentage of genetically confirmed WD cases presented peptide levels above the cutoffs, therefore representing a border line zone of patients that will likely still be difficult to diagnose or rule out as WD. Owing to the retrospective nature of the sample collection, available clinical data were not extensive and information about current medical treatments were not detailed. Regardless, the possibility of a new diagnostic test to add to the WD toolkit available to practitioners not familiar with WD, is appealing and ultimately beneficial to patients. This study and the significance of the ATP7B peptides is timely as it positions itself in the middle of an ongoing debate about the full penetrance of WD,14Sandahl T.D. Laursen T.L. Munk D.E. et al.The prevalence of Wilson's disease: an update.Hepatology. 2020; 71: 722-732Crossref PubMed Scopus (24) Google Scholar the role of extra hepatic ATP7B copper transporter on clinical manifestations,15Pierson H. Muchenditsi A. Kim B.E. et al.The function of ATPase copper transporter ATP7B in intestine.Gastroenterology. 2018; 154: 168-180.e5Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar and the significance of ATP7B variants on disease phenotype. Genetic testing and the knowledge to interpret these data remain incomplete. This study on ATP7B peptides opens clinical and research opportunities aiming to correlate peptide levels with disease severity and phenotype on larger populations. As suggested by the authors, integrating peptide levels into a validated diagnostic scoring system which includes copper metabolism parameters and genetic testing should be a major research focus and could lead to improved phenotypic and prognostic patient characterization. Ultimately, the proposed approach may be helpful to diagnose both adult and pediatric cases of WD. In summary, expanding the diagnostic toolkit of WD is a priority and this study offers an additional option that could have a role as an initial screening or confirmatory test and will ensure that fewer diagnoses are delayed or missed. Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson DiseaseGastroenterologyVol. 160Issue 7PreviewBoth existing clinical criteria and genetic testing have significant limitations for the diagnosis of Wilson disease (WD), often creating ambiguities in patient identification and leading to delayed diagnosis and ineffective management. ATP7B protein concentration, indicated by direct measurement of surrogate peptides from patient dried blood spot samples, could provide primary evidence of WD. ATP7B concentrations were measured in patient samples from diverse backgrounds, diagnostic potential is determined, and results are compared with biochemical and genetic results from individual patients. Full-Text PDF Open Access" @default.
• W3137162300 created "2021-03-29" @default.
• W3137162300 creator A5035509372 @default.
• W3137162300 date "2021-06-01" @default.
• W3137162300 modified "2023-09-27" @default.
• W3137162300 title "Expanding the Diagnostic Toolkit of Wilson Disease with ATP7B Peptides" @default.
• W3137162300 cites W1796552583 @default.
• W3137162300 cites W1996610030 @default.
• W3137162300 cites W2077167146 @default.
• W3137162300 cites W2087820907 @default.
• W3137162300 cites W2737416585 @default.
• W3137162300 cites W2760279858 @default.
• W3137162300 cites W2763505612 @default.
• W3137162300 cites W2789798326 @default.
• W3137162300 cites W2890069589 @default.
• W3137162300 cites W2891947356 @default.
• W3137162300 cites W2914945422 @default.
• W3137162300 cites W2920986554 @default.
• W3137162300 cites W2970468982 @default.
• W3137162300 cites W2995563930 @default.
• W3137162300 cites W3133004451 @default.
• W3137162300 doi "https://doi.org/10.1053/j.gastro.2021.03.025" @default.
• W3137162300 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33753100" @default.
• W3137162300 hasPublicationYear "2021" @default.
• W3137162300 type Work @default.
• W3137162300 sameAs 3137162300 @default.
• W3137162300 citedByCount "1" @default.
• W3137162300 countsByYear W31371623002021 @default.
• W3137162300 crossrefType "journal-article" @default.
• W3137162300 hasAuthorship W3137162300A5035509372 @default.
• W3137162300 hasBestOaLocation W31371623001 @default.
• W3137162300 hasConcept C126322002 @default.
• W3137162300 hasConcept C2776231509 @default.
• W3137162300 hasConcept C2779134260 @default.
• W3137162300 hasConcept C41008148 @default.
• W3137162300 hasConcept C70721500 @default.
• W3137162300 hasConcept C71924100 @default.
• W3137162300 hasConcept C86803240 @default.
• W3137162300 hasConceptScore W3137162300C126322002 @default.
• W3137162300 hasConceptScore W3137162300C2776231509 @default.
• W3137162300 hasConceptScore W3137162300C2779134260 @default.
• W3137162300 hasConceptScore W3137162300C41008148 @default.
• W3137162300 hasConceptScore W3137162300C70721500 @default.
• W3137162300 hasConceptScore W3137162300C71924100 @default.
• W3137162300 hasConceptScore W3137162300C86803240 @default.
• W3137162300 hasFunder F4320332161 @default.
• W3137162300 hasIssue "7" @default.
• W3137162300 hasLocation W31371623001 @default.
• W3137162300 hasLocation W31371623002 @default.
• W3137162300 hasLocation W31371623003 @default.
• W3137162300 hasOpenAccess W3137162300 @default.
• W3137162300 hasPrimaryLocation W31371623001 @default.
• W3137162300 hasRelatedWork W1920876971 @default.
• W3137162300 hasRelatedWork W2082482010 @default.
• W3137162300 hasRelatedWork W2392678261 @default.
• W3137162300 hasRelatedWork W2581099805 @default.
• W3137162300 hasRelatedWork W2748952813 @default.
• W3137162300 hasRelatedWork W2765379856 @default.
• W3137162300 hasRelatedWork W2899084033 @default.
• W3137162300 hasRelatedWork W4230652811 @default.
• W3137162300 hasRelatedWork W4233480692 @default.
• W3137162300 hasRelatedWork W4320040405 @default.
• W3137162300 hasVolume "160" @default.
• W3137162300 isParatext "false" @default.
• W3137162300 isRetracted "false" @default.
• W3137162300 magId "3137162300" @default.
• W3137162300 workType "article" @default.