Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors.
Adult
Arthritis, Rheumatoid
/ blood
Biomarkers
/ blood
C-Reactive Protein
/ metabolism
Female
Humans
Kynurenine
/ analogs & derivatives
Longitudinal Studies
Male
Middle Aged
Nutritional Status
Pyridoxal Phosphate
/ blood
Treatment Outcome
Tumor Necrosis Factor Inhibitors
/ therapeutic use
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
Vitamin B 6
/ blood
Vitamin B 6 Deficiency
/ blood
Xanthurenates
/ blood
3-hydroxykynurenine: xanthurenic acid ratio
TNFα inhibitors
functional vitamin B-6 status
pyridoxal 5′-phosphate
rheumatoid arthritis
Journal
The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
received:
15
05
2018
revised:
18
06
2018
accepted:
03
01
2018
entrez:
4
5
2019
pubmed:
6
5
2019
medline:
3
4
2020
Statut:
ppublish
Résumé
A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed. We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors. We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNFα inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression. At baseline PLP was inversely correlated with CRP (ρ = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (ρ = 0.46, P < 0.001), CRP (ρ = 0.36, P < 0.001), and ultrasonography scores (ρ = 0.29-0.35, P ≤ 0.003). After 3 mo treatment, the change (a 33% overall reduction) in DAS28 was related to changes in both PLP (ß = -0.28, P = 0.01) and HK: XA (ß = 0.33, P < 0.001). Good responders (45%) according to EULAR criteria experienced a 31% increase in PLP (P = 0.003) and an 11% decrease in HK: XA (P = 0.1), whereas nonresponders (24%) experienced a 25% increase in HK: XA (P = 0.02). Two independent measures of vitamin B-6 status confirm an association with disease activity in RA patients. The association of HK: XA with disease activity may also imply perturbations in kynurenine metabolism in RA. This trial was registered at helseforskning.etikkom.no as 2011/490.
Sections du résumé
BACKGROUND
A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed.
OBJECTIVE
We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors.
METHODS
We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNFα inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression.
RESULTS
At baseline PLP was inversely correlated with CRP (ρ = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (ρ = 0.46, P < 0.001), CRP (ρ = 0.36, P < 0.001), and ultrasonography scores (ρ = 0.29-0.35, P ≤ 0.003). After 3 mo treatment, the change (a 33% overall reduction) in DAS28 was related to changes in both PLP (ß = -0.28, P = 0.01) and HK: XA (ß = 0.33, P < 0.001). Good responders (45%) according to EULAR criteria experienced a 31% increase in PLP (P = 0.003) and an 11% decrease in HK: XA (P = 0.1), whereas nonresponders (24%) experienced a 25% increase in HK: XA (P = 0.02).
CONCLUSION
Two independent measures of vitamin B-6 status confirm an association with disease activity in RA patients. The association of HK: XA with disease activity may also imply perturbations in kynurenine metabolism in RA. This trial was registered at helseforskning.etikkom.no as 2011/490.
Identifiants
pubmed: 31050750
pii: S0022-3166(22)16613-7
doi: 10.1093/jn/nxz001
doi:
Substances chimiques
Biomarkers
0
TNF protein, human
0
Tumor Necrosis Factor Inhibitors
0
Tumor Necrosis Factor-alpha
0
Xanthurenates
0
3-hydroxykynurenine
27723548JL
Kynurenine
343-65-7
xanthurenic acid
58LAB1BG8J
Pyridoxal Phosphate
5V5IOJ8338
Vitamin B 6
8059-24-3
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
770-775Informations de copyright
Copyright © American Society for Nutrition 2019.