Stolk J N, Boerbooms A M, De Abreu R A, Kerstens P J, de Koning D G, de Graaf R, Mulder J, van de Putte L B
Department of Rheumatology, University Hospital Nijmegen, Netherlands.
Ann Rheum Dis. 1996 Oct;55(10):733-8. doi: 10.1136/ard.55.10.733.
Purine enzyme activities may predict the effectiveness of azathioprine treatment and be associated with increased deaths from infectious diseases. In rheumatoid arthritis, patients show variable responses to azathioprine and a higher percentage of death is caused by infections. The aim of the study was to investigate possible rheumatoid arthritis associated abnormalities of purine enzyme activities by measuring several of these enzymes in patients with recent onset rheumatoid arthritis before treatment with disease modifying antirheumatic drugs or prednisone.
23 patients with recent onset rheumatoid arthritis and 28 healthy controls were studied. Activities of the enzymes 5'-nucleotidase, purine nucleoside phosphorylase (PNP), hypoxanthine guanine phosphoribosyltransferase (HGPRT), and thiopurine methyltransferase (TPMT) were measured. Assessment of disease activity and blood sampling for routine measurements and HLA typing were done simultaneously.
Purine enzyme activities did not differ between patients and healthy controls. Enzyme activities had no significant relations with indices of disease activity or rheumatoid factor titre or with the rheumatoid arthritis associated HLA types. Activity of 5'nucleotidase decreased with age (P < or = 0.05) and was lower by about 27% (P = 0.007) in males than in females.
In rheumatoid arthritis patients, neither the variability in azathioprine effectiveness nor the increased death rate from infections can be explained by pre-existing abnormalities in the activities of the purine enzymes 5'-nucleotidase, PNP, HGPRT, or TPMT at an early stage of the disease, before disease modifying antirheumatic drugs or prednisone treatment. Besides adjustment for age, results of studies involving purine 5' nucleotidase activity should also be adjusted for sex.
嘌呤酶活性可能预测硫唑嘌呤治疗的有效性,并与传染病死亡风险增加相关。在类风湿关节炎中,患者对硫唑嘌呤的反应各异,且较高比例的死亡由感染所致。本研究旨在通过测定初发类风湿关节炎患者在使用改善病情抗风湿药物或泼尼松治疗前的几种嘌呤酶活性,来探究类风湿关节炎可能相关的嘌呤酶活性异常情况。
对23例初发类风湿关节炎患者和28名健康对照者进行研究。测定了5'-核苷酸酶、嘌呤核苷磷酸化酶(PNP)、次黄嘌呤鸟嘌呤磷酸核糖转移酶(HGPRT)和硫嘌呤甲基转移酶(TPMT)的活性。同时进行疾病活动度评估以及用于常规检测和HLA分型的血液采样。
患者与健康对照者之间的嘌呤酶活性无差异。酶活性与疾病活动度指标、类风湿因子滴度或类风湿关节炎相关的HLA类型均无显著关联。5'-核苷酸酶活性随年龄降低(P≤0.05),男性比女性低约27%(P = 0.007)。
在类风湿关节炎患者中,在使用改善病情抗风湿药物或泼尼松治疗之前的疾病早期阶段,嘌呤酶5'-核苷酸酶、PNP、HGPRT或TPMT活性预先存在的异常,既无法解释硫唑嘌呤有效性的变异性,也无法解释感染导致的死亡率增加。除了对年龄进行校正外,涉及嘌呤5'-核苷酸酶活性的研究结果还应进行性别校正。