Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV-infected patients
Abstract
An alternative pathway of Trp metabolism involves the conversion of Trp to kynurenine by indoleamine-2,3-dioxygenase, which leads to synthesis of the neurotoxin, quinolinic acid. This study explores the relationship of indoleamine-2,3-dioxygenase activity with stages of HIV infection. Sera from 206 HIV-positive and 72 seronegative subjects were analyzed for Trp and kynurenine. The kynurenine-to-Trp (KT) ratio was calculated. The mean KT ratio of seronegative controls was 36.6 ± 10.9, and the median ratio was 34.9. The upper limit of the seronegative KT ratio, defined as mean + 2 SD, was 58.4. Patients with HIV infection showed a reciprocal relationship between the KT ratio, the CD4 count, and the stage of the disease. The median KT ratios for asymptomatic and AIDS patients were 50.5 and 117.0, respectively. This study shows that the serum Trp concentration is markedly decreased and that the kynurenine concentration is increased with immune stimulation in HIV infection. This may lead to changes in quinolinic acid and explain some of the pathogenesis of AIDS dementia.
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Several viral infections, including HIV, HCV, and HSV, increase activation of the kynurenine pathway, which is implicated in the neurological and cognitive impairments of patients with HIV, HCV, and HSV.
“Several viral infections, including HIV [19], HCV [20], and HSV [21] increase activation of the KP, which interestingly is implicated in the neurological and cognitive impairments of patients with HIV, HCV, and HSV [21,22].”
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- Authors
- Huengsberg, M., Winer, J. B., Gompels, M., Round, R., Ross, J., & Shahmanesh, M.
- Affiliations
- Department of GU Medicine, Whittall Street Clinic, Birmingham B4-6 DH, UK
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Royal Victoria Infirmary (GB)
- Corresponding author
- Huengsberg, Mia
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-04-01
- Volume
- 44
- Issue
- 4
- Pages
- 858-862
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2131301672
- Cited by
- 172
- References
- 0
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 21 · 2023: 3 · 2022: 4 · 2021: 12 · 2020: 10 · 2019: 6 · 2018: 6 · 2017: 7 · 2016: 13 · 2015: 14 · 2014: 7 · 2013: 8 · 2012: 2
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- kynurenine/tryptophan ratio, tryptophan metabolism, indoleamine 2,3-dioxygenase, quinolinic acid, HIV infection, AIDS, CD4 count, disease progression, serum tryptophan, neurotoxicity, HIV-associated dementia
- MeSH terms
- Acquired Immunodeficiency Syndrome, Adult, Aged, Female, Humans, Kynurenine, Male, Middle Aged, Peripheral Nervous System Diseases, Prospective Studies, Retrospective Studies, Tryptophan, Tryptophan Oxygenase, AIDS Dementia Complex, HIV Seronegativity, CD4 Lymphocyte Count
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