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The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis

OBJECTIVES: The exact etiology of pruritus in chronic cholestasis is unknown. Pruritus intensity does not correlate with common biochemical indices and there is a lack of biomarkers guiding diagnosis and treatment. We explored profiles of bile acids (BA) and muricholic acids (MCA) as well as autotax...

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Autores principales: Meinel, Katharina, Szabo, Doloresz, Dezsofi, Antal, Pohl, Sina, Strini, Tanja, Greimel, Theresa, Aguiriano-Moser, Victor, Haidl, Harald, Wagner, Martin, Schlagenhauf, Axel, Jahnel, Jörg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130722/
https://www.ncbi.nlm.nih.gov/pubmed/35633951
http://dx.doi.org/10.3389/fped.2022.903360
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author Meinel, Katharina
Szabo, Doloresz
Dezsofi, Antal
Pohl, Sina
Strini, Tanja
Greimel, Theresa
Aguiriano-Moser, Victor
Haidl, Harald
Wagner, Martin
Schlagenhauf, Axel
Jahnel, Jörg
author_facet Meinel, Katharina
Szabo, Doloresz
Dezsofi, Antal
Pohl, Sina
Strini, Tanja
Greimel, Theresa
Aguiriano-Moser, Victor
Haidl, Harald
Wagner, Martin
Schlagenhauf, Axel
Jahnel, Jörg
author_sort Meinel, Katharina
collection PubMed
description OBJECTIVES: The exact etiology of pruritus in chronic cholestasis is unknown. Pruritus intensity does not correlate with common biochemical indices and there is a lack of biomarkers guiding diagnosis and treatment. We explored profiles of bile acids (BA) and muricholic acids (MCA) as well as autotaxin (ATX) antigen levels as potential circulating biomarkers of pruritus in pediatric patients. METHODS: In 27 pediatric cholestatic patients [autoimmune sclerosing cholangitis (ASC) n = 20 (with pruritus n = 6, without pruritus n = 14); progressive familial intrahepatic cholestasis (PFIC) n = 7 (with pruritus n = 5, without pruritus n = 2)] and 23 age-matched controls pruritus was assessed by a visual analog scale of pruritus (PVAS). We obtained profiles of serum human BA including MCA using a mass-spectrometry assay and ATX antigen levels with a commercial ELISA. RESULTS: PFIC and ASC patients exhibited significantly higher BA-, and MCA levels, than healthy controls, but only PFIC patients showed elevated ATX antigen levels higher [median: 1,650 ng/ml, interquartile rang (IQR): 776.9–3,742] compared to controls (median: 315.9 ng/ml, IQR: 251.1–417.2; PFIC p = 0.0003). ASC patients with pruritus showed only a minor increase in total BA (tBA) levels (median: 76.5 μmol/L, IQR: 54.7–205), but strikingly higher T-conjugated BA (median: 16.4 μmol/L, IQR: 8.9–41.4) and total MCA (tMCA) (median: 1.15 μmol/L, IQR: 0.77–2.44) levels compared to ASC patients without pruritus (tBA median: 24.3 μmol/L, IQR: 16.2–80.8; p < 0.0408; T-conjugated BA median: 1.3 μmol/L, IQR: 0.8–4.9; p = 0.0023; tMCA median: 0.30 μmol/L, IQR: 0.13–0.64, p = 0.0033). BA/MCA profiles distinctly differed depending on presence/absence of pruritus. Different from PFIC patients, ATX antigen levels were not significantly elevated in ASC patients with (median: 665.8 ng/ml, IQR: 357.8–1,203) and without pruritus (median: 391.0 ng/ml, IQR: 283.2–485.6). In ASC patients, tBA, tMCA, and ATX antigen levels did not correlate with pruritus severity. CONCLUSION: Despite the same underlying disease, pediatric ASC patients with pruritus exhibit significantly altered BA profiles and MCA levels compared to ASC patients without pruritus. ATX antigen levels seem to have little diagnostic or prognostic meaning in ASC patients. An increased ATX activity alone seems not to be causal for pruritus genesis in ASC patients. CLINICAL TRIAL REGISTRATION: [www.drks.de], identifier [DRKS00026913].
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spelling pubmed-91307222022-05-26 The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis Meinel, Katharina Szabo, Doloresz Dezsofi, Antal Pohl, Sina Strini, Tanja Greimel, Theresa Aguiriano-Moser, Victor Haidl, Harald Wagner, Martin Schlagenhauf, Axel Jahnel, Jörg Front Pediatr Pediatrics OBJECTIVES: The exact etiology of pruritus in chronic cholestasis is unknown. Pruritus intensity does not correlate with common biochemical indices and there is a lack of biomarkers guiding diagnosis and treatment. We explored profiles of bile acids (BA) and muricholic acids (MCA) as well as autotaxin (ATX) antigen levels as potential circulating biomarkers of pruritus in pediatric patients. METHODS: In 27 pediatric cholestatic patients [autoimmune sclerosing cholangitis (ASC) n = 20 (with pruritus n = 6, without pruritus n = 14); progressive familial intrahepatic cholestasis (PFIC) n = 7 (with pruritus n = 5, without pruritus n = 2)] and 23 age-matched controls pruritus was assessed by a visual analog scale of pruritus (PVAS). We obtained profiles of serum human BA including MCA using a mass-spectrometry assay and ATX antigen levels with a commercial ELISA. RESULTS: PFIC and ASC patients exhibited significantly higher BA-, and MCA levels, than healthy controls, but only PFIC patients showed elevated ATX antigen levels higher [median: 1,650 ng/ml, interquartile rang (IQR): 776.9–3,742] compared to controls (median: 315.9 ng/ml, IQR: 251.1–417.2; PFIC p = 0.0003). ASC patients with pruritus showed only a minor increase in total BA (tBA) levels (median: 76.5 μmol/L, IQR: 54.7–205), but strikingly higher T-conjugated BA (median: 16.4 μmol/L, IQR: 8.9–41.4) and total MCA (tMCA) (median: 1.15 μmol/L, IQR: 0.77–2.44) levels compared to ASC patients without pruritus (tBA median: 24.3 μmol/L, IQR: 16.2–80.8; p < 0.0408; T-conjugated BA median: 1.3 μmol/L, IQR: 0.8–4.9; p = 0.0023; tMCA median: 0.30 μmol/L, IQR: 0.13–0.64, p = 0.0033). BA/MCA profiles distinctly differed depending on presence/absence of pruritus. Different from PFIC patients, ATX antigen levels were not significantly elevated in ASC patients with (median: 665.8 ng/ml, IQR: 357.8–1,203) and without pruritus (median: 391.0 ng/ml, IQR: 283.2–485.6). In ASC patients, tBA, tMCA, and ATX antigen levels did not correlate with pruritus severity. CONCLUSION: Despite the same underlying disease, pediatric ASC patients with pruritus exhibit significantly altered BA profiles and MCA levels compared to ASC patients without pruritus. ATX antigen levels seem to have little diagnostic or prognostic meaning in ASC patients. An increased ATX activity alone seems not to be causal for pruritus genesis in ASC patients. CLINICAL TRIAL REGISTRATION: [www.drks.de], identifier [DRKS00026913]. Frontiers Media S.A. 2022-05-11 /pmc/articles/PMC9130722/ /pubmed/35633951 http://dx.doi.org/10.3389/fped.2022.903360 Text en Copyright © 2022 Meinel, Szabo, Dezsofi, Pohl, Strini, Greimel, Aguiriano-Moser, Haidl, Wagner, Schlagenhauf and Jahnel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Meinel, Katharina
Szabo, Doloresz
Dezsofi, Antal
Pohl, Sina
Strini, Tanja
Greimel, Theresa
Aguiriano-Moser, Victor
Haidl, Harald
Wagner, Martin
Schlagenhauf, Axel
Jahnel, Jörg
The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis
title The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis
title_full The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis
title_fullStr The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis
title_full_unstemmed The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis
title_short The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis
title_sort covert surge: murine bile acid levels are associated with pruritus in pediatric autoimmune sclerosing cholangitis
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130722/
https://www.ncbi.nlm.nih.gov/pubmed/35633951
http://dx.doi.org/10.3389/fped.2022.903360
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