Daily urinary neopterin excretion as an immunological marker of disease activity in multiple sclerosis
Daily urinary neopterin excretion as an immunological marker of disease activity in multiple sclerosis
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DOI：
10.1093/brain/120.1.1
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发表时间：
1997-01-01
期刊：
影响因子：
14.5
通讯作者：
Thompson, EJ
中科院分区：
文献类型：
--
作者：
Giovannoni, G;Lai, M;Thompson, EJ
本研究的目的是评估新蝶呤，干扰素γ（IFN-γ）诱导的巨噬细胞活性的标志物作为多发性硬化症患者炎症的可能替代标志物。在10名原发进展型（PP）、10名复发缓解型（RR）和II型继发进展型（SP）多发性硬化患者和14名正常对照（NC）受试者中，每天测量尿新蝶呤与肌酐比值（UNCR），持续时间长达12周。在排除与感染相关的测量后，患者的个体平均UNCR的中位数显著高于对照组（所有患者P < 0.001，三组患者均P < 0.01）; PT、RR、SP患者和对照组的中位UNCR（和四分位距）分别为187（135-231）、187（165-277）、218（164-517）和134（97-152）μ mol/mol。同样，患者UNCR高于正常值的天数比例中位数更高（所有患者P < 0.001，各组P <0.01）; PP、RR、SP患者和对照组的中位数百分比（和四分位距）分别为16（6-62）、28（21-36）、49（14-86）和0（0-6）%。他们在连续UNCR测量中也比对照组有更多的峰（所有患者P < 0.001，每组P < 0.01）;平均值+/-SD峰值/受试者/月分别为：2.1+/-1.8; 3.0+/-1.7; PP、RR、SP患者和对照组分别为3.3+/-2.3和0.2+/-0.6。在研究期间，9名患者发生9次复发，所有复发均与新蝶呤排泄增加有关，其倾向于大于与复发无关的天数。9次复发中有3次是在上呼吸道感染之前。在研究期间发生感染的13名患者中，有8名患者在感染后长达6周的时间内观察到新蝶呤排泄增加，明显长于对照组感染后的时间。这证实了感染是多发性硬化症中有症状和无症状疾病活动的有效诱导物，并进一步支持IFN-γ在多发性硬化症发病机制中的关键作用。进行性和复发性多发性硬化患者尿新蝶呤排泄增加，因此有可能作为多发性硬化疾病活动性炎症成分的替代标志物。
The aim of this study was to assess neopterin, a marker of interferon gamma (IFN-gamma) induced macrophage activity as a possible surrogate marker of inflammation in patients with multiple sclerosis. Urinary neopterin to creatinine ratios (UNCRs) were measured daily in 10 primary progressive (PP), 10 relapsing remitting (RR) and II secondary progressive (SP) patients with multiple sclerosis, and 14 normal control (NC) subjects, for periods of up to 12 weeks. After excluding measurements related to infection, the median of the individuals' average UNCRs was significantly higher in patients than in controls (P < 0.001 for all patients and P < 0.01 for each of the three groups of patients); the median UNCRs (and interquartile ranges) were 187 (135-231), 187 (165-277), 218 (164-517) and 134 (97-152) mu mol/mol for PT, RR, SP patients and controls, respectively. Similarly, patients had a greater median proportion of days with a UNCR above normal (P < 0.001 for all patients and P < 0.01 for each group); the median percentages (and interquartile ranges) were 16 (6-62), 28 (21-36), 49 (14-86) and 0 (0-6)% for PP, RR, SP patients and controls, respectively. They also had a greater number of peaks in their serial UNCR measurements than controls (P < 0.001 for all patients and P < 0.01 for each group); the means+/-SD peaks/subject/month were: 2.1+/-1.8; 3.0+/-1.7; 3.3+/-2.3 and 0.2+/-0.6 for PP, RR, SP patients and controls, respectively Nine relapses occurred in nine patients during the study and all were associated with increased neopterin excretion, which tended to be greater than that on days not associated with a relapse. Three of the nine relapses were preceded by an upper respiratory tract infection. In eight out of 13 patients who had infections during the study, increased neopterin excretion was noted for periods of up to 6 weeks post-infection, significantly longer than that which occurred after infections in controls. This confirms infection as a potent inducer of symptomatic and asymptomatic disease activity in mutiple sclerosis, and provides further support of a pivotal role for IFN-gamma in the pathogenesis of mutiple sclerosis. Urinary neopterin excretion is increased in patients with both progressive and relapsing mutiple sclerosis, and therefore has potential as a surrogate marker of the inflammatory component of mutiple sclerosis disease activity.