High inter-individual variability of serum xanthine oxidoreductase activity in IBD patients

ABSTRACT

Objectives: Thiopurines play an essential role in the management of inflammatory bowel diseases (IBD, i.e. Crohn's disease and ulcerative colitis). Over the past decade, several strategies to optimize treatment with thiopurines have been evaluated, including co-administration of allopurinol, a xanthine-oxidoreductase (XO) inhibitor, to low-dose thiopurine therapy. We aimed to assess the inter-individual variability of XO-activity between IBD-patients.

Methods: We assessed XO activity in serum of IBD-patients of two medical centers in The Netherlands using the Amplex® Red Xanthine/Xanthine Oxidase Assay Kit, which measures the superoxide formation in a coupled reaction to the red-fluorescent oxidation product, resofurine.

Results: We observed a high inter-individual variability of XO-activity in 119 patients, with a median activity of 16 µU/ml/hour (range 1–85 µU/ml/hour). The XO-activity was influenced by gender (male 19.5 vs. female 14.0 µU/ml/hour, p < 0.01), patient's age (Pearson's correlation r = 0.21, p = 0.02) and duration of IBD (r = 0.23, p = 0.01). The XO activity was not affected by the type of IBD, smoking status, body mass index or (type of) thiopurine use (p > 0.05).

Conclusions: There is a high inter-individual variability of XO-activity in IBD-patients; XO-activity is positively associated with male gender and patient's age.

KEYWORDS:

• Inflammatory bowel disease
• thiopurines
• azathioprine
• mercaptopurine
• xanthine oxidoreductase
• allopurinol
• Crohn's disease
• ulcerative colitis

Conflicts of interest

None to declare

Acknowledgements

We thank Nienke Losekoot for execution of the assay and Kees Smid and Richard Honeywell for their contribution in the interpretation.

Authorship contributions

Participated in research design: NdB, AvB

Conducted experiments: MS, TH

Contributed new reagents or analytic tools: GP

Performed data analysis: BM, MS, TH

Wrote or contributed to the writing of the manuscript: BM, MS, TH, RL, JK, GP, CM, AvB, NdB