Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis
J. Clin. Invest. Ricardo T. Paniagua, et al. 116:2633 doi:10.1172/JCI28546 [Go to this article.]

Figure 5
Imatinib inhibits B cell proliferation and Ig production in vitro and autoreactive B cell epitope spreading in vivo. (A) B cells from naive DBA/1 mice were stimulated with 50 μg/ml IgM or 5 μg/ml LPS in the presence of 0–10 μM imatinib. After 48 hours, B cells were pulsed with [³H]thymidine for 18 hours. Data represent mean cpm ± SEM of quadruplicates and are representative of 3 independent experiments. incorp., incorporation. (B) B cells stimulated with LPS (5 μg/ml) were cocultured with 0–10 μM imatinib, and IgM production was measured by ELISA. *P < 0.05, **P < 0.01, ***P < 0.001 compared with stimulated cells without imatinib. (C) Synovial array profiling of serum autoantibodies derived from mice with CIA treated with PBS (n = 7) or 100 mg/kg imatinib (n = 7) (day 49). Synovial microarrays containing candidate autoantigens in RA and CIA were incubated with 1:150 dilutions of mouse sera; autoantibody binding was detected with Cy3-labeled anti-mouse IgG/M secondary antibody; and arrays were scanned to quantify autoantibody binding to each antigen feature. SAM was applied to identify antigen features with statistical differences in autoantibody reactivity in samples derived from PBS-treated mice as compared with imatinib-treated mice (false discovery rate, 0.06). Cluster software was used to order results for the mice and the SAM-identified antigen features, and TreeView software was used to display the resulting clusters of autoantibody reactivity as a heatmap. Red represents positive reactivity, yellow intermediate reactivity, and blue lack of reactivity. Numbers in the key represent digital fluorescence intensity units.