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Clinical Chemistry 44: 858-862, 1998;
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(Clinical Chemistry. 1998;44:858-862.)
© 1998 American Association for Clinical Chemistry, Inc.

General Clinical Chemistry

Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV-infected patients

Mia Huengsberg1,a, John B. Winer2, Mark Gompels3, Rachel Round1, Jonathan Ross1, and Mohsen Shahmanesh1

1 Department of GU Medicine, Whittall Street Clinic, Birmingham B4-6 DH, UK.

2 Department of Neurology, University Hospital Birmingham NHS Trust, Birmingham B15-2 TH, UK.

3 Department of Immunology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
a Address correspondence to this author at: Department of GU Medicine, Whittall Street Clinic, Birmingham, B4 6DH, UK. Fax 44-121-237-5729; e-mail: Mia{at}di-ren.demon.co.uk.

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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