Brain, Vol 120, Issue 1 1-13, Copyright © 1997 by Oxford University Press
G Giovannoni, M Lai, D Kidd, JW Thorpe, DH Miller, AJ Thompson, G Keir, M Feldmann and EJ Thompson
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 11 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) mumol/mol for PP, 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 percentage (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 te 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.
ARTICLES
Daily urinary neopterin excretion as an immunological marker of disease activity in multiple sclerosis
Neuroimmunology Unit, Institute of Neurology, London, UK.
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