What is measured?

The method includes protein precipitation by trichloroacetic acid, which oxidises 7,8-dihydroneopterin to neopterin, and measures total neopterin, which is higher than concentrations obtained using assays that measure only neopterin.
Method(s): LC-MS/MS (1).

What is neopterin?

Neopterin, a pyrazino-pyrimidine compound, is synthesized by monocytes and macrophages in response to interferon-𝛾 (IFN-γ) produced by activated T cells. Both total neopterin and neopterin reflect cellular immune response, because IFN-γ induces a step that precedes formation of 7,8-dihydroneopterin in the neopterin pathway. Increased concentrations are observed in infections by viruses, including human immunodeficiency virus (HIV), infections by intracellular bacteria and parasites, autoimmune diseases, malignant tumour diseases and in allograft rejection episodes. Neopterin in serum/plasma shows a strong, positive relation to total homocysteine and to the kynurenine/tryptophan ratio (KTR) (2).


Assessment of cellular immune response.

Specimen, collection and processing

Matrix: Plasma and serum. Neopterin increases (up to 100%) in samples with hemolysis.
Volume: Minimum volume is 60 µL, but 200 µL is optimal and allows reanalysis.
Preparation: Samples should be put on ice, and protected from exposure to ultraviolet light and sunlight.


Frozen, on dry ice and protected from exposure to ultraviolet light and sunlight. (for general instruction on transportation, click here)

Reported values, interpretation

Total neopterin correlates strongly with neopterin in urine and plasma, and with plasma KTR. Neopterin and total neopterin are of equal value for the assessment of immune activation (3).
Reported values: 5-50 nmol/L.
Intraclass correlation coefficient (ICC): 0.60.


1. 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.
2. Capuron, L., Geisler, S., Kurz, K., Leblhuber, F., Sperner-Unterweger, B., and Fuchs, D. (2014). Activated immune system and inflammation in healthy ageing: Relevance for tryptophan and neopterin Metabolism. Curr Pharm Des 20, 6048-057.
3. Fuchs, D., Milstien, S., Krämer, A., Reibnegger, G., Werner, E.R., Goedert, J.J., Kaufman, S., and Wachter, H. (1989). Urinary neopterin concentrations vs total neopterins for clinical utility. Clin Chem 35, 2305-07.

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