The effect of etanercept therapy on adrenal steroid metabolism in juvenile idiopathic arthritis: a steroid metabolomics approach

Bibliographic Details
Title: The effect of etanercept therapy on adrenal steroid metabolism in juvenile idiopathic arthritis: a steroid metabolomics approach
Authors: Yonatan Butbul Aviel, Ariel Keinan, Michaela F. Hartmann, Stefan A. Wudy, Dov Tiosano
Source: Pediatric Rheumatology Online Journal, Vol 21, Iss 1, Pp 1-9 (2023)
Publisher Information: BMC, 2023.
Publication Year: 2023
Collection: LCC:Pediatrics
LCC:Diseases of the musculoskeletal system
Subject Terms: Juvenile idiopathic arthritis, Steroid, Metabolomics, GC-MS, Anti-TNFα, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935
More Details: Abstract Objective To evaluate the impact of anti-tumor necrosis factor-alpha (TNFα: etanercept [Etanercept ®]) therapy on adrenal activity in juvenile idiopathic arthritis (JIA) . Method Eleven JIA patients aged 12 ± 6.2 years with a disease duration of 6.3 ± 5.2 years were enrolled. They were treated once weekly with etanercept (0.8 mg/kg) for 3 ± 2.8 years. Urine samples for gas chromatography-mass spectrometry steroid hormone analysis were collected before, and 1 and 3 days after etanercept injection and compared to age- and sex-matched healthy controls. Results The levels of 21 of the 31 metabolites were low before etanercept treatment. Those 21 metabolites included 4 C19 steroids (androgens), 5 C C21 steroid hormone intermediates, 10 cortisol metabolites, and 2 corticosterone metabolites. One day after treatment, only 5 of the 21 metabolite levels remained low. They included 2 C19 metabolites, 2 C21 steroid metabolites and 1 cortisol metabolite β –Cortol (β-Cl). Three days after treatment, the only metabolites levels that continued to be low were 2 C19 metabolite, 2 C21 steroid hormone intermediates and 1 cortisol metabolite α-Cortol (a-Cl), while the remaining 15 metabolites had already normalized after 1 day. Dehydroepiandrosterone-sulfate and 17-hydroxypregnenolone metabolite levels were the last ones to recover. Urinary metabolite ratios reflecting cytochrome P450 CYP21A2 (21-hydroxylase) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzymatic activitieswere lower in JIA patients than in controls, although significant was not reached. Conclusion Almost all of the pre-etanercept treatment cortisol urinary metabolite levels were significantly lower than normal, and almost all rose to normal values by 1 day after treatment. The therapeutic effect of anti-TNFα treatment in JIA may be related to its effect on the restoration of adrenal function and cortisol levels.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1546-0096
Relation: https://doaj.org/toc/1546-0096
DOI: 10.1186/s12969-023-00813-y
Access URL: https://doaj.org/article/ab16052cbfc74e84a748f6121263206b
Accession Number: edsdoj.b16052cbfc74e84a748f6121263206b
Database: Directory of Open Access Journals
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More Details
ISSN:15460096
DOI:10.1186/s12969-023-00813-y
Published in:Pediatric Rheumatology Online Journal
Language:English