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TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis.

ABSTRACT: BACKGROUND:Children with juvenile idiopathic arthritis (JIA) have impaired physical abilities. TNF-? plays a crucial role in this pathogenesis, but it is also involved in the use of lipids and muscle health. Objective of this study was to explore substrate oxidation and impact of TNF blockade on energy metabolism in children with JIA as compared to healthy children. METHODS:Fifteen non-TNF-blockaded and 15 TNF-blockaded children with JIA and 15 healthy controls were matched by sex, age, and Tanner stage. Participants completed a submaximal incremental exercise test on ergocycle to determine fat and carbohydrate oxidation rates by indirect calorimetry. RESULTS:The maximal fat oxidation rate during exercise was lower in JIA children untreated by TNF blockade (134.3?±?45.2?mg.min-?1) when compared to the controls (225.3?±?92.9?mg.min-?1, p?=?0.007); but was higher in JIA children under TNF blockade (163.2?±?59.0?mg.min-?1, p?=?0.31) when compared to JIA children untreated by TNF blockade. At the same relative exercise intensities, there was no difference in carbohydrate oxidation rate between three groups. CONCLUSIONS:Lipid metabolism during exercise was found to be impaired in children with JIA. However, TNF treatment seems to improve the fat oxidation rate in this population. TRIAL REGISTRATION:In ClinicalTrials.gov, reference number NCT02977416 , registered on 30 November 2016.

SUBMITTER: Rochette E

PROVIDER: S-EPMC6647146 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis.

Rochette Emmanuelle E Bourdier Pierre P Pereira Bruno B Doré Eric E Birat Anthony A Ratel Sébastien S Echaubard Stéphane S Duché Pascale P Merlin Etienne E

Pediatric rheumatology online journal 20190722 1

<h4>Background</h4>Children with juvenile idiopathic arthritis (JIA) have impaired physical abilities. TNF-α plays a crucial role in this pathogenesis, but it is also involved in the use of lipids and muscle health. Objective of this study was to explore substrate oxidation and impact of TNF blockade on energy metabolism in children with JIA as compared to healthy children.<h4>Methods</h4>Fifteen non-TNF-blockaded and 15 TNF-blockaded children with JIA and 15 healthy controls were matched by sex ...[more]

PMID: 31331342

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Project description:BackgroundHaptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs.MethodsPlasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP).ResultsAt 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001).ConclusionHp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.

Dataset Information

TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis.

Publications

TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis.

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