Kerstens P J, Stolk J N, De Abreu R A, Lambooy L H, van de Putte L B, Boerbooms A A
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Arthritis Rheum. 1995 Jan;38(1):142-5. doi: 10.1002/art.1780380122.
Azathioprine (AZA) metabolism largely parallels the endogenous purine pathways. To date, thiopurine methyltransferase (TPMT) deficiency has been reported as a cause of AZA-related bone marrow toxicity in 1 patient with rheumatoid arthritis (RA). We therefore studied purine enzyme activities in 3 patients with RA who experienced AZA-related bone marrow toxicity.
Lymphocyte activity of purine nucleoside phosphorylase and 5'-nucleotidase (5NT) and erythrocyte activity of TPMT, key enzymes in thiopurine catabolism, were measured in 3 RA patients who had experienced AZA-related bone marrow toxicity and in 16 RA patients without signs of toxicity despite at least 6 months of treatment with AZA.
Two patients with AZA-related bone marrow toxicity were found to have a TPMT deficiency, 1 partial and 1 total. In the third patient, 5NT activity was found to be well below the lowest level observed in the control subjects.
All 3 patients with severe AZA-related bone marrow toxicity had abnormal purine enzyme activities. Deficiency of purine enzymes, including TPMT and 5NT, may be a cause of AZA-related bone marrow toxicity in patients with RA.
硫唑嘌呤（AZA）的代谢在很大程度上与内源性嘌呤代谢途径相似。迄今为止，已有报道称1例类风湿关节炎（RA）患者中，硫嘌呤甲基转移酶（TPMT）缺乏是AZA相关骨髓毒性的一个原因。因此，我们研究了3例发生AZA相关骨髓毒性的RA患者的嘌呤酶活性。
测定了3例发生AZA相关骨髓毒性的RA患者以及16例尽管接受了至少6个月的AZA治疗但无毒性迹象的RA患者的淋巴细胞中嘌呤核苷磷酸化酶和5'-核苷酸酶（5NT）的活性，以及红细胞中硫嘌呤分解代谢的关键酶TPMT的活性。
发现2例发生AZA相关骨髓毒性的患者存在TPMT缺乏，1例部分缺乏，1例完全缺乏。在第3例患者中，发现5NT活性远低于对照组观察到的最低水平。
所有3例发生严重AZA相关骨髓毒性的患者嘌呤酶活性均异常。包括TPMT和5NT在内的嘌呤酶缺乏可能是RA患者中AZA相关骨髓毒性的一个原因。
