Biopterin and Neopterin in human multiple sclerosis
A: Biopterin and neopterin concentrations in plasma or serum in
two cohorts of patients with multiple sclerosis (MS-1 n = 102; MS-2 n =
14 with repeated samples over time) as compared to biopterin/neopterin
in four cohorts of healthy control subjects of different ages. The
gender distribution was 2:1 women/men in MS patients as well as in
healthy cohorts. The time courses are shown in C. The box shows the
interquartile range, the line is the median, whiskers show minimum to
maximum. Each scatter represents one subject except in the right plot,
where each scatter is one sample. Data were compared with two-way ANOVA
for ”pterin X group” and subsequent posthoc t-test for group using an
adjustment of alpha according to and Šidák. *P < 0.05, **P
< 0.01, ***P < 0.001.
B: Serum biopterin concentrations of MS cohort-1 categorized
according to ICD10 criteria as compared to healthy controls. Each
scatter is a patient or healthy control. The box shows the interquartile
range, the line is the median, whiskers show minimum to maximum. Data
were compared with two-way ANOVA for ”pterin X group” and subsequent
posthoc t-test for group using an adjustment of alpha according to and
Šidák. *P < 0.05, **P < 0.01, ***P <
0.001.
C: Time courses of serum biopterin and neopterin concentrations
in 14 MS patients with complicated MS course. The X-axis shows the days
since diagnosis, which was day zero. The dashed lines show the mean
biopterin (B) or neopterin (N) concentration in healthy controls. Arrows
point to relapses (R) without or with steroid medication (R/S). Patients
received fingolimod (FG), natalizumab (Ntx) or rituximab (Rtx) as
indicated. Biopterin was persistently low, not obviously in association
with relapse or medication.
D: Plasma concentrations of biopterin in a human whole blood
assay upon stimulation with lipopolysaccharide, LPS versus vehicle
(mean, SD). Biopterin levels drop over time in LPS stimulated samples.
Each scatter is one healthy donor (n = 13), whose blood samples were
split in two, one for LPS the other as control. The middle panel shows
the paired analyses of the subject’s LPS and vehicle samples at
different time points. Paired data were compared by paired t-tests and
time courses per 2-way ANOVA for ”time X treatment”.
Figure 2