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