IVIG treatment significantly abrogates the arthritis clinical score
CIA is a mouse model which imitates rheumatoid arthritis in genetically prone human RA patients, in which inflammation leads to the joint destruction. We investigated the effect of IVIG treatment in CIA mice and compared its efficacy with CIA mice treated with PBS (vehicle) or non-treated CIA mice.
Both IVIG and PBS treatments started when the baseline arthritic score was almost 3. We observed a significantly lower marginal arthritis score in IVIG-treated mice as compared to marginal arthritis score of PBS-treated mice or non-treated mice (P < 0.001) as illustrated in Fig. 1. Repeated measures ANOVA analysis revealed a significant difference between the treatment groups mean arthritis score over time F=30.224, P <0.0001 (lower-bound adjusted). Marginal arthritis score of the different studied groups was as follow: The IVIG group had the lowest arthritis score marginal mean of 4.128 95% CI (3.995, 4.262), in comparison to 5.78 95% CI (5.56, 6.01) for non-treated CIA mice, and 5.62 95%CL (5.45, 5.77) for PBS treated CIA mice P <0.0001 (Bonferroni adjusted). The significantly lower arthritis score lasted until the mice were sacrificed at day 48 (Fig.1). No significant change in mice body weight was documented overtime in the three studied groups, P >0.05 (data not shown).
Analyzing the clinical score at day 27 after the boost administration (day 48 from day 0 of diseases induction ), showed score of 4.48±0.98 in CIA mice treated with IVIG, P <0.001, whereas a score of 8.09 ±2.13 and 7.51±1.05 for PBS or non-treated CIA mice was observed, respectively (Fig.2).
H&E staining of the joints tissue sections from the IVIG-treated mice as described in Fig.3A, demonstrates a significantly less synovial hyperplasia, no inflammatory process or neutrophil infiltration, normal cartilage layer and muscle structure, typical bone organization and uninflamed fat tissue, as in healthy non injected mice (Fig.3B). Whereas in CIA mice treated with PBS (Fig.3C) and in non-treated CIA mice (Fig.3D), a massive infiltration of neutrophils can be observed as well as bone and joint destruction.