Urinary eicosanoid and tyrosine derivative concentrations in patients with vasculitides

Higashi, Noritaka; Mita, Haruhisa; Taniguchi, Masami; Turikisawa, Naomi; Higashi, Ai; Ozawa, Yoshinori; Tohma, Shigeto; Arimura, Kimiyoshi; Akiyama, Kazuo

doi:10.1016/j.jaci.2004.09.027

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 114, Issue 6 , Pages 1353-1358, December 2004

Urinary eicosanoid and tyrosine derivative concentrations in patients with vasculitides

Noritaka Higashi, MD, PhD
- From the Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa
- Third Department of Internal Medicine, Kagoshima University School of Medicine, Sakuragaoka, Kagoshima
- Reprint requests: Noritaka Higashi, MD, Scheeles väg1, PO Box 287, National Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Haruhisa Mita, PhD
- From the Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa
Masami Taniguchi, MD, PhD
- From the Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa
Naomi Turikisawa, MD, PhD
- From the Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa
Ai Higashi, MD
- From the Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa
- Third Department of Internal Medicine, Kagoshima University School of Medicine, Sakuragaoka, Kagoshima
Yoshinori Ozawa, MD, PhD
- From the Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa
Shigeto Tohma, MD, PhD
- From the Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa
Kimiyoshi Arimura, MD, PhD
- Third Department of Internal Medicine, Kagoshima University School of Medicine, Sakuragaoka, Kagoshima
Kazuo Akiyama, MD
- From the Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa

Received 23 April 2004; received in revised form 3 August 2004; accepted 20 September 2004.

Sagamihara, Kanagawa, and Kagoshima, Japan

Background

Vasculitides are classified on the basis of the type of cell involved, namely, eosinophilic vasculitides such as Churg-Strauss syndrome (CSS) and noneosinophilic vasculitides. However, knowledge on inflammatory mediators and oxidative tissue damage associated with vasculitides is insufficient.

Objective

We measured the urinary concentrations of inflammatory mediators and tyrosine derivatives to assess biomarkers associated with the pathophysiology of vasculitides.

Methods

Urine was collected from 9 patients with CSS during acute exacerbation and during clinical remission, 24 patients with rheumatoid arthritis in stable condition, and 8 patients with vasculitis diseases (VDs) during acute exacerbation. Leukotriene E₄ (LTE₄), 9α,11β prostaglandin F₂, and eosinophil-derived neurotoxin (EDN) concentrations were determined by enzyme immunoassay. 3-Bromotyrosine (BrY) and 3-chlorotyrosine (ClY) concentrations were determined by gas chromatography-mass spectrometry.

Results

The urinary LTE₄, EDN, BrY, and ClY concentrations were significantly higher in the patients with CSS during acute exacerbation than in healthy control subjects and, except for urinary ClY concentration, significantly decreased during clinical remission. The urinary EDN and BrY concentrations were significantly higher in patients with CSS during acute exacerbation than in patients with VD during acute exacerbation. Only urinary LTE₄ concentration was significantly different between the patients with rheumatoid arthritis in stable condition and the patients with VD during acute exacerbation.

Conclusion

Oxidative tissue damage caused by eosinophil peroxidase is a pathophysiological characteristic of eosinophil-associated diseases such as CSS. Urinary LTE₄ concentration may reflect a pathophysiological event involved in eosinophilic and noneosinophilic vasculitides. Cysteinyl-leukotriene pathways are potential therapeutic targets for small-vessel vasculitides.

Key words: Churg-Strauss syndrome, vasculitides, 3-bromotyrosine, 3-chlorotyrosine, leukotriene E₄

Abbreviations used: ANCA, Antineutrophil cytoplasmic autoantibody, BrY, 3-Bromotyrosine, ClY, 3-Chlorotyrosine, cr, Creatinine, CSS, Churg-Strauss syndrome, cysLT, Cysteinyl-leukotriene, EDN, Eosinophil-derived neurotoxin, EPO, Eosinophil peroxidase, HC, Healthy control, HOBr, Hypobromous acid, LT, Leukotriene, MPA, Microscopic polyangiitis, PG, Prostaglandin, RA, Rheumatoid arthritis, TA, Temporal arteritis, VD, Vasculitis disease, WG, Wegener granulomatosis