fig7

Figure 7. (A and B) CCL2 levels were suppressed in five of the eight phase IIA subjects. CCL2 levels in subjects 103, 201, and 202 were elevated above that observed with HC; in the remaining subjects, CCL2 expression levels were low and their levels remained within HC levels; (C and D) Treg/IL-2 combination therapy suppressed IL-18 levels in six of the eight phase IIA subjects. IL-18 levels in two phase IIA subjects, 103 and 202, were elevated throughout the study; the remaining phase IIA subjects’ IL-18 levels were low and only rose following cessation of Treg therapy; (E and F) 4-HNE levels in phase IIA subjects 103 and 201 were elevated; 4-HNE levels in the remaining six phase IIA subjects were low and only rose following cessation of therapy; (G and H) MDA levels were refractory to Treg/IL-2 therapy in seven of the eight phase IIA subjects; only subject 115 had low MDA levels throughout the study; (I and J) Only phase IIA subject, 201, had increased Nf-L levels and those levels increased throughout the study; the remaining phase IIA subjects Nf-L levels remained within HC levels; (K and L) Only one phase IIA subject had increased levels of pNf-H. The remaining seven phase IIA subjects remained within HC levels throughout the study. Red line = mean value of each analyte in HC. Black lines ± one standard deviation of each analyte level in HC. The phase IIA trial consisted of a 24-week randomized, double-blind, placebo-controlled trial (RCT) followed by a 24-week ascending dose open-label extension (OLE)^[24]. Blue arrows indicate when subjects received Treg/IL-2 therapy during the RCT and the red arrows indicate when subjects received Treg/IL-2 therapy during the OLE. Four subjects, 103, 115, 202, and 204, were randomized to the placebo group during the RCT but received Treg/IL-2 infusions during the OLE. Three subjects, 114, 201, and 203, were randomized to the active group and received Treg/IL-2 therapy during the RCT and later received Treg/IL-2 infusions during the OLE. Two subjects, 205 and 206, were directly enrolled in the OLE and received Treg/IL-2 therapy^[24].