Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Kynurenine pathway is altered in patients with SLE and associated with severe fatigue
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Show others and affiliations
2018 (English)In: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 5, no 1, article id e000254Article in journal (Refereed) Published
Abstract [en]

Objective: Fatigue has been reported as the most disturbing symptom in a majority of patients with SLE. Depression is common and often severe. Together these symptoms cause significant morbidity and affect patients with otherwise relatively mild disease. Tryptophan and its metabolites in the kynurenine pathway are known to be important in several psychiatric conditions, for example, depression, which are often also associated with fatigue. We therefore investigated the kynurenine pathway in patients with SLE and controls.

Methods: In a cross-sectional design plasma samples from 132 well-characterised patients with SLE and 30 age-matched and gender-matched population-based controls were analysed by liquid chromatography tandem mass spectrometry to measure the levels of tryptophan and its metabolites kynurenine and quinolinic acid. Fatigue was measured with Fatigue Severity Scale and depression with Hospital Anxiety and Depression Scale. SLE disease activity was assessed with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Results: The kynurenine/tryptophan ratio, as a measure of indoleamine 2,3-dioxygenase (IDO) activity, was increased in patients with SLE. Patients with active disease (SLEDAI >= 6) showed lower tryptophan levels compared with controls (54 mu M, SD=19 vs 62 mu M, SD=14, p=0.03), although patients with SLE overall did not differ compared with controls. Patients with SLE had higher levels of tryptophan metabolites kynurenine (966 nM, SD=530) and quinolinic acid (546 nM, SD=480) compared with controls (kynurenine: 712 nM, SD=230, p=0.0001; quinolinic acid: 380 nM, SD=150, p=0.001). Kynurenine, quinolinic acid and the kynurenine/tryptophan ratio correlated weakly with severe fatigue (r(s)=0.34, r(s)=0.28 and r(s)=0.24, respectively) but not with depression.

Conclusions: Metabolites in the kynurenine pathway are altered in patients with SLE compared with controls. Interestingly, fatigue correlated weakly with measures of enhanced tryptophan metabolism, while depression did not. Drugs targeting enzymes in the kynurenine pathway, for example, IDO inhibitors or niacin (B12) supplementation, which suppresses IDO activity, merit further investigation as treatments in SLE.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018. Vol. 5, no 1, article id e000254
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-166400DOI: 10.1136/lupus-2017-000254ISI: 000495994400006PubMedID: 29868176OAI: oai:DiVA.org:umu-166400DiVA, id: diva2:1379710
Available from: 2019-12-17 Created: 2019-12-17 Last updated: 2019-12-17Bibliographically approved

Open Access in DiVA

fulltext(664 kB)18 downloads
File information
File name FULLTEXT01.pdfFile size 664 kBChecksum SHA-512
b9e46bb54286911dce94f814ff53ecbbe54b3dc0481519f71b0bc0d36287251701fe697596a3a3cec8bcdd80ec24dd282703515354ea67ffe84779d7c90017e5
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Pettersson, SusanneSurowiec, IzabellaHedenström, MattiasTrygg, Johan
By organisation
Department of Chemistry
In the same journal
Lupus Science and Medicine
Rheumatology and Autoimmunity

Search outside of DiVA

GoogleGoogle Scholar
Total: 18 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 39 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf