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Urinary Adenosine and Aminoimidazolecarboxamide Excretion in Methotrexate-Treated Patients With Psoriasis
Joseph E. Baggott, PhD;
Sarah L. Morgan, MD, RD;
W. Mitchell Sams, MD;
Joel Linden, PhD
Arch Dermatol. 1999;135:813-817.
Background We hypothesized that low-dose methotrexate treatment for patients with psoriasis would block purine biosynthesis at the step catalyzed by aminoimidazolecarboxamide (AICA) ribotide transformylase and would inhibit adenosine metabolism as evidenced by increased urinary levels of AICA and adenosine, respectively. Eight patients collected a 24-hour urine specimen on the day before their methotrexate dose and the next day during their methotrexate dose. Eight age- and sex-matched controls also collected a 24-hour urine sample. Urinary AICA and adenosine were assayed by spectrophotometric and radioimmune assays, respectively; means are reported as micromole per millimole of creatinine and were compared by the paired t test (1-tailed).
Observations Mean AICA excretion increased from 1.30 µmol/mmol on the day before to 1.85 µmol/mmol on the day during methotrexate dosing (P<.01). Mean adenosine values increased from 0.68 to 1.07 µmol/mmol, (P<.03). Controls had mean AICA and adenosine levels of 1.29 and 0.50 µmol/mmol, respectively. During the day of methotrexate dosing, patients had higher mean AICA and adenosine levels when compared with controls (P<.01). Mean AICA levels increased from 1.36 to 2.06 µmol/mmol (P<.025), and mean adenosine levels increased from 0.72 to 1.25 µmol/mmol (P<.025) in 5 patients showing improvement in clinical disease activity. In contrast, 3 patients with no change or worsening in clinical disease activity had smaller increases.
Conclusions Methotrexate treatment of patients with psoriasis inhibits AICA ribotide transformylase and adenosine metabolism. Since adenosine is a T-lymphocyte toxin, it may be partially responsible for the immunosuppressive effect.
From the Departments of Nutrition Sciences, Schools of Health Related Professions, Medicine, and Dentistry (Drs Baggott and Morgan), Medicine (Dr Morgan), and Dermatology (Dr Sams), School of Medicine, University of Alabama, Birmingham; and the Department of Medicine, Molecular Physiology, and Biological Physics, School of Medicine, University of Virginia, Charlottesville (Dr Linden).
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