Measuring the Kynurenine to Tryptophan ratio by ELISA: Highlights from our customers' research

Ten years ago, we introduced the first research ELISA kits designed to easily measure Kynurenine (Kyn) and Tryptophan (Trp) concentrations in biological fluids.

With a minimal sample volume requirement of just 20 μL, our kits have been widely used to calculate the kynurenine/tryptophan ratio in various sample types, including cell culture supernatants, blood samples, and tissue homogenates from both animal and human origins.

Here, we highlight key applications and research achievements made by our customers using our ELISA kits.

Infectious diseases

Influenza: In 2021, a US team documented reduced kynurenine pathway metabolism in the plasma of critically ill patients, as well as in the lungs of aged mice infected with influenza.

Tuberculosis/HIV co-infection: In 2020, Gascua?Adu-Gyamfi et al. established plasma kynurenine/tryptophan ratio as a diagnostic? biomarker of pulmonary tuberculosis in both HIV-infected and uninfected individuals. The team compared our ELISA kit to MS, and recommended the ELISA approach for frontline clinical diagnosis. Results were confirmed in a 2021 study in pregnant women living with HIV.

Venezuelan equine encephalitis virus: In 2024 paper, a team from the University of Texas measured the KYN/TRP ratio in brain homogenates of mice infected with Venezuelan equine encephalitis virus (VEEV), demonstrating elevated IDO1 activity correlated with cognitive impairment.

HIV & diffuse large B-cell lymphoma: A 2024 study in 76 patients with Diffuse large B-cell lymphoma (DLBCL) reported elevated plasma Kynurenine to Tryptophan ratio, especially in patients with HIV.

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Neurological & psychiatric disorders

Schizophrenia: in 2021, a Spanish team investigated tryptophan metabolism along the serotoninergic and kynurenine pathways in animal model of schizophrenia. Using our ELISA kits in frontal cortex homogenates, they found a significant decrease in 5-HT levels and dysregulated kynurenine pathway, with elevated levels of neurotoxin Quinolinic acid, which could be reversed with the administration of antipsychotic?drug paliperidone. Read paper

Bipolar depression: In June 2024, a Belgian team measured Tryptophan, Kynurenine, Kynurenic acid and Quinolinic acid in the plasma of 37 patients with bipolar depression (BD-D) using our ELISA kits. They reported lower concentrations of kynurenine pathway metabolites in BD-D patients than in healthy controls, and found that baseline levels of Quinolinic acid predicted symptom improvement in patients treated with theta burst stimulation.

Depression & cognitive decline associated with metabolic syndrome: In 2024, a research team from Italy reported high kynurenine to tryptophan ratio in the serum from mice subjected to chronic mild stress or high blood glucose, and even higher levels in animals combining both regimens. Overall, their paper demonstrates that both hyperglycemia (a key feature of diabetes) and chronic stress (a possible factor of major depression) contribute to the upregulation of the kynurenine pathway, leading to hippocampal damage.

Mood & Sleep Disorders: In 2022, a Spanish team supplemented rats with a saffron extract one hour before sleep. They reported a reduction in serum kynurenine levels and increased levels of circulating melatonin, with stable levels of tryptophan.

Immuno-Oncology

Assessment of IDO1 inhibitors: In two separate studies (Watanabe et al., 2020; Wang et al., 2023), researchers used our kits to assess the functionality of IDO inhibitors, especially in combination with anti-PD-1 antibodies. In the two above-mentioned publications, investigators measured kynurenine and tryptophan in tumor homogenates and serum samples from syngeneic tumor models, reporting higher tryptophan concentrations in mice treated with IDO inhibitors, as expected.

Mechanisms of cancer immune evasion: In 2024, a Chinese team demonstrated that the overexpression of polyadenylate-binding protein PABPC1L in renal cell carcinoma is associated with resistance to immune checkpoint blockade and upregulation of IDO1. They used our kits to validate their hypothesis in vitro, measuring the Kynurenine/Tryptophan ratio in the supernatant of PABPLC1L / IDO1 knock-down renal carcinoma cells (Renca).

Blood biomarker: In 2019, a Spanish team released a paper evaluating potential predictive blood biomarkers of clinical response to anti-PD1 immunotherapy in non-small-cell lung cancer. Using our kit to determine the KYN/TRP ratio in patient's plasma samples, they found plasma IDO activity to be associated with disease progression. In 2023, a German team reported that the KYN/TRP ratio might be used as a serum biomarker of metastasis in oral squamous cell carcinoma. Interestingly, they found that serum KYN/TRP ratio was correlated with IDO1 expression in PBMC, but not in epithelial tumor cells.

IDO expression in iTreg: In 2023, a Greek team reported that the in vitro hypomethylation of T cells unlocks myeloid suppressor genes, resulting in the upregulation of IDO1 and CCL17/22 genes, and higher kynurenine concentrations in cell supernatant measured by ELISA.

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Other inflammatory disorders

Lupus: A study released in May 2024 by a Japanese team reported that patients with systemic lupus erythematosus with high serum levels of anti-ribosomal P protein antibody also exhibited higher concentrations of inflammatory cytokines and accelerated tryptophan metabolism through the Kynurenine pathway, with an elevated Kynurenine to Tryptophan ratio.

Atherosclerosis: Starting from transcriptomic data from carotid plaques and arteries from patients with atherosclerosis, a team from the Karolinska Institute evidenced in 2020 a shift in tryptophan metabolism along the kynurenine pathway in symptomatic patients, characterized by the upregulation of the quinolinic acid branch and a downregulation of kynurenic acid branch. A paper currently in pre-print also used our kits in the supernatant of an in vitro model of macrophages exposed to atherosclerotic plaque, as well as in the plasma of atherosclerotic patients. Their results show that the activation of the kynurenine pathway in macrophages in the context of atherosclerosis, involving LXR signaling, leads to kynurenine overproduction and increased expression of endothelial adhesion molecules, thus contributing to the progression of the disease.

Obesity: In 2022, a team from the Medical University of Vienna used our ELISA kits to quantify plasma concentrations of tryptophan, kynurenine, and serotonin in young patients with severe obesity. They reported a significant correlation between tryptophan catabolism via the kynurenine pathway and BMI score and body fat mass.

Sepsis/Endotoxic death: In 2022, a Japanese team showed in Cell Reports that the central administration of C-type lectin Reg3γ can save mice treated with LPS from endotoxic death through the inhibition of microglial IDO1, preventing the aberrant production of neurotoxin quinolinic acid and the subsequent metabolic arrest of neurons in the brain. The team extensively used our ELISA kits in this study, monitoring kynurenine pathway metabolites in mice's CSF, sera, brain homogenates, and cell culture samples.

Since 2016, nearly 100 papers have been published using our ELISA kits for Tryptophan, Kynurenine, Kynurenic acid, Quinolinic Acid, Serotonin, Melatonin and 5-HIAA.

Learn more about our ELISA kits and antibodies to assess Tryptophan Metabolism along the kynurenine pathway

As shown in this review, our kits were used a variety of in vitro, in vivo, and ex vivo samples. Feel free to ask Dominique Bodet, PhD if you need advice!

Non-exhaustive list of contributors to the papers cited in this review:

Soo Jung Cho augustine choi Chanida Fongsaran Kelly Dineley Slobodan Paessler Irma Cisneros Karina MacDowell Eva Munarriz-Cuezva Annelies Dellink Kaat Hebbrecht Dieter Zeeuws Chris Baeken Chris Bervoets Manuel Morrens Violette Coppens micaela gliozzi Anna Rita Coppoletta Catherine Belzung Simone Gaedicke Elena Guffart Elke Firat Jianqin Lu Virginia Pardo Marqués Ma Teresa Agulló Ortu?o Dr. med. Dr. med. dent. Ann-Kristin Struckmeier Memnon Lysandrou Alexandros Spyridonidis Paul Costeas Daniel Ketelhuth charles THOMAS Damien LELEU Julia Lischka Kenta Maruyama M.D., Ph.D.