BEVITAL AS

Targeted Metabolomics Services

Neopterin

neopt
Updated 21/12/2022

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: 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).

Indication(s)

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.

Transportation

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.

Literature

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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Cardiometabolic
Inflammation
Microbiome
Nutrition
Categories

Amino acids, amino acid catabolites, acylcarnitines, TCA metabolites, ketone bodies, AGEs



Kynurenines, ratio-derived metabolites, proteins





SCFAs, indoles, choline metabolites, amino acid derived





B-vitamins, functional markers, and methyl donors, fat-soluble vitamins, essential amino acids, meat & fish intake, tobacco use & coffee intake
Biomarkers
65
18
20
41
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Amino acids: Alanine, Arginine, Asparagine, Aspartic acid, Glutamic acid, Glutamine, Glycine, Histidine, Isoleucine, Kynurenine, Leucine, Lysine, Methionine, Ornithine, Phenylalanine, Proline, Sarcosine, Serine, Threonine, Total cysteine, Tryptophan, Tyrosine, Valine

Amino acids and catabolites: 2-Aminoadipic acid, 2-Hydroxybutyrate, 3-Hydroxysiobutyrate, α-Hydroxyglutaric acid, β-Alanine, β-Aminoisobutyrate, β-Hydroxy B-methylbutyric acid, Phenylacetylglutamine

Acylcarnities: BB, C0, C2, C3, C3, DC, C4, C4-OH , C4-DC , iC5 , C5-DC, C5:1 , C6 , C8, C10, C12, C14 , C14-OH, C16, C16-OH, C18 , C18-OH, C18:1, C18:2

TCA metabolites: α-Ketoglutarate, Citrate, Fumarate, Isocitrate, Lactate, Malate, Pyruvate, Ketone bodies, 3-Hydroxybutyrate, Acetoacetate

AGEs: Carboxyethyllysine, Carboxymethyllysine

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Kynurenines: Kynurenine, Kynurenic acid, Quinaldic acid, Anthranilic acid, 3-Hydroxykynurenine, Xanthurenic acid, 3-Hydroxyanthranilic acid, Picolinic acid, Quinolinic acid, Nicotinic acid, Nicotinamide, N1-methylnicotinamide

Neopterin

Proteins: C-Reactive protein, Calprotectin, Serum Amyloid A

Ratio-derived: Kynurenine/tryptophan ratio, PAr index (PLP, PL, PA)

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SCFAs: Acetate, Butyrate, Formate, Isobutyrate, Isovalerate, Propionate, Valerate, α-Methylbutyrate

Indoles: 3-Indoxyl sulfate, Imidazole propionate, Indole-3-acetamide, Indole-3-acetate, Indole-3-aldehyde, Indole-3-lactate, Indole-3-propionate

Choline metabolites: Choline ,Betaine, DMG, TMAO

Amino acid derived: Phenylacetylglutamine

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B-vitamins, functional markers, and methyl donors: 4-Pyridoxic acid, Betaine, Choline, Cobalamin, Flavin mononucleotide, Folate, Methylmalonic acid, N1-methylnicotinamide, Nicotinamide, Nicotinic acid, Pyridoxal, Pyridoxal 5-phosphate, Pyridoxine, Riboflavin, Thiamine, Thiamine monophosphate, Total homocysteine

Fat-soluble vitamins: 25-hydroxy vitamin D2, 25-hydroxy vitamin D3, α-Tocopherol (Vit. E), All-trans retinol (Vit. A), Phylloquinone (Vit. K1), y-Tocopherol (Vit. E)

Essential amino acids: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

Meat and fish intake: 1-Methylhistidine, 3-Methylhistidine, B-Alanine, Creatine, Creatinine, TMAO

Tobacco use and coffee intake: Cotinine, Trans-3-hydroxycotinine, Trigonelline

Volume (ul)
150
100
200
200
Analytical technique
GC- and LC-MS/MS
LC- and MALDI-MS
GC- and LC-MS/MS
GC- and LC-MS/MS
Turnaround time (weeks)
1
1
1
1

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