Kynurenine and the kynurenine/tryptophan ratio



Method(s): GC-MS/MS (1), LC-MS/MS (2).

What is measured on the same platform, click here.
Platform B: MMA, tHcy, tCys, Met, Ser, Gly, Cysta, Sarc, His, Trp, Kyn, (KTR), HK, KA, XA, AA, HAA, NA, PA, Figlu, Orn, Asp, Glu, Lys, Ala, Phe, Ile, Leu, Pro, Val, Asn, Gln, Thr, Tyr, aKG, 3HIB, aHB, bHB, AcAc
Platform D: PLP, PL, PA, (PAr), PN, Thi, TMP, Ribo, FMN, Cysta, Neopt, Trp, Kyn, (KTR), KA, AA, HK, XA, (HK/XA), HAA, Pic, QA, NA, NAM, mNAM, Cot, OHCot, Trig

What is kynurenine?

Kynurenine (Kyn) is formed from the essential amino acid tryptophan (Trp). One enzyme involved in this reaction is indolamine 2,3-dioxygenase (IDO), which is upregulated by various cytokines, in particular INF-gamma. This explains why immune activation leads to formation of kynurenine and depletion of tryptophan. Thus, the kynurenine/tryptophan ratio (KTR) is a marker of cellular (Th-1 type) immune response (3).

Performance of the assay (LC-MS/MS)

Lower limit of detection (LOD) (Kyn/Trp): 7/4 nmol/L.
Within-day CV: 3-5/3-4 %; between-day CV: 6-9/6 %.

Indication(s)

Assessment of cellular immune response.

Specimen, collection and processing

Patient/subject: Reduced kynurenine levels are observed after reduced dietary intake of tryptophan.
Matrix: EDTA plasma and serum.
Volume: Minimum volume is 60 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: The blood sample must be centrifuged and the plasma/serum fraction put on ice, and frozen. Kynurenine and tryptophan are stable.

Transportation; for general instruction on transportation, click here.

Frozen, on dry ice.

Reported values, interpretation

Reported values: Kyn: 1.0-2.9 µmol/L; Trp: 43-89 µmol/L.
Intraclass correlation coefficients (ICC) (Kyn/Trp/KTR): 0.68/0.51/0.67.

Literature

1. Midttun, Ø., McCann, A., Aarseth, O., Krokeide, M., Kvalheim, G., Meyer, K., and Ueland, P.M. (2016). Combined measurement of 6 fat-soluble vitamins and 26 water-soluble functional vitamin markers and amino acids in 50 μL of serum or plasma by high-throughput mass spectrometry. Anal Chem 88, 10427-436.
2. Midttun, O., Hustad, S., and Ueland, P.M. (2009). Quantitative profiling of biomarkers related to B-vitamin status, tryptophan metabolism and inflammation in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Sp 23, 1371-79.
3. Ueland, P. M., A. McCann, O. Midttun and A. Ulvik (2017) Inflammation, vitamin B6 and related pathways. Mol Aspects Med 53:10-27.