Fig. 1: Disease scores and histological analysis in response to oral immunotherapy (OIT) in CIA mice.

a Disease scores (left panel) and incidence (right panel) were evaluated at the indicated time points for naïve (grey), CIA (red) and CIA-OIT (blue). OIT consisted of administration of undenatured type II collagen by oral gavage 3 times a week, starting 2 weeks before induction of arthritis. Cumulative disease scores were given for each limb, 0 = no disease and 4 = highest score. Each dot represents the mean of individual mice and error bars show SEM (n = 15 for CIA, n = 16 for OIT groups, n = 9 for naïve mice, data from 2 independent experiments). Statistical significance was determined by one-way ANOVA; *p < 0.05, ***p < 0.001 between CIA and naïve, #p < 0.05, ##p < 0.01 comparing CIA and OIT groups. Disease incidence was calculated by dividing the number of cases by the total number of mice in the group at the indicated times. b Paw width (left panel) and weight change (percentage of initial weight, right panel) were evaluated at the indicated time points. Each dot represents the mean of individual mice, error bars show SEM (n = 15 for CIA, n = 7 for OIT asymptomatic, n = 9 for OIT symptomatic, n = 9 for naïve mice, data from 2 independent experiments). Statistical significance was determined by one-way ANOVA; *p < 0.05, ***p < 0.01,***p < 0.001, ns = non-significant. c Hind paws were collected at the end of the experiment (day 34) for each mouse, sectioned, and stained with haematoxylin and eosin for histological analysis. Images show one representative mouse (Disease score = median for each group). Superimposed dotted lines show bone limits; scale bar = 500 μm. d Cell infiltration, pannus formation, cartilage and bone damage were quantified for individual mice in hematoxilin/eosin-stained sections. Dot plots show histological scores (from 0 to 4, 0 = healthy tissue, 4 = highest possible score). Individual dots represent individual paws (n = 32 for CIA, n = 8 for OIT asymptomatic, and n = 24 for OIT symptomatic, data collected from 2 independent experiments). Bars show the mean value for each group. Statistical significance was determined by the Kruskal–Wallis test; **p < 0.01, ***p < 0.001. The percentage of mice with no sign of pathology (green) for the indicated parameter is shown in vertical column graphs.