Blood levels of kynurenines, interleukin-23 and soluble human leucocyte antigen-G at different stages of Huntington's disease

Forrest, C. M., Mackay, G. M., Stoy, N., Spiden, S. L., Taylor, R., Stone, T. W. and Darlington, L.G. (2010) Blood levels of kynurenines, interleukin-23 and soluble human leucocyte antigen-G at different stages of Huntington's disease. Journal of Neurochemistry, 112(1), pp. 112-122. (doi: 10.1111/j.1471-4159.2009.06442.x)

Abstract

There is substantial evidence that abnormal concentrations of oxidised tryptophan metabolites, produced via the kynurenine pathway, contribute to progressive neurodegeneration in Huntington's disease. We have now examined the blood levels of these metabolites in patients at different stages of Huntington's disease, assessed both in terms of clinical disease severity and numbers of CAG repeats. Close relatives of the patients were included in the study as well as unrelated healthy controls. Levels of lipid peroxidation products, the pro-inflammatory cytokine interleukin (IL)-23 and the soluble human leucocyte antigen-G (sHLA-G) were also measured. There were lower levels of tryptophan and a higher kynurenine : tryptophan ratio, indicating activation of indoleamine-2,3-dioxygenase, in the most severely affected group of patients, with increased levels of IL-23 and sHLA-G. Marked correlations were noted between IL-23 and the patient severity group, anthranilic acid levels and the number of CAG repeats, and between anthranilic acid and IL-23, supporting our previous evidence of a relationship between anthranilic acid and inflammatory status. Tryptophan was negatively correlated with symptom severity and number of CAG repeats, and positively correlated with sHLA-G. The results support the proposal that tryptophan metabolism along the kynurenine pathway in Huntington's disease is related to the degree of genetic abnormality, to clinical disease severity and to aspects of immunopathogenesis.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Forrest, Dr Caroline and Stone, Professor Trevor and Mackay, Dr Gillian
• Authors: Forrest, C. M., Mackay, G. M., Stoy, N., Spiden, S. L., Taylor, R., Stone, T. W., and Darlington, L.G.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Neurochemistry
• Publisher: Wiley
• ISSN: 0022-3042
• ISSN (Online): 1471-4159
• Published Online: 20 October 2009
• Copyright Holders: Copyright © 2009 The Authors
• First Published: First published in Journal of Neurochemistry 112(1):112-122
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.