Page 171 - Haematologica August 2018

Dexamethasone promotes tolerance to factor VIII
Results
Administration of Dex during initial FVIII exposure reduces the initial anti-FVIII immune response in both E17KO/hMHC and E16KO mice
Our first aim was to determine the ability of Dex to pre- vent the anti-FVIII immune response when administered during initial antigen exposure. FVIII was administered alone or in combination with Dex for five consecutive days (week zero, Figure 1A,B). At week five, 6% of E17KO/hMHC FVIII+Dex mice compared to 33% of
E17KO/hMHC FVIII mice had evidence of plasma anti-FVIII IgG (P=0.0050, Figure 2A). Furthermore, FVIII+Dex mice that developed anti-FVIII IgG had lower antibody titers than FVIII mice (Figure 2B). A similar effect was observed in E16KO mice, with 77% of E16KO FVIII+Dex mice com- pared to 100% of E16KO FVIII mice showing evidence of plasma anti-FVIII IgG (P=0.0485, Figure 2C), and FVIII+Dex mice having significantly lower anti-FVIII IgG titers than FVIII mice (P=0.0063, Figure 2D). Although not statistically significant, a similar trend was observed when looking at inhibitor incidence and activity in E16KO mice (Figure 2E,F).
AB
P=0.0050
CD
E
P=0.0132
P=0.0699
F P=0.1536
G
P=0.0150 H
Figure 3. Administration of Dex during initial FVIII exposure induces tolerance to FVIII in E17KO/hMHC mice, even when co-administered with LPS. A. Anti-FVIII IgG incidence, B. anti- FVIII IgG titers, C. FVIII inhibitor incidence and D. FVIII inhibito- ry activity following re-exposure to FVIII in E17KO/hMHC mice initially exposed to FVIII or FVIII+Dex and with no evidence of anti-FVIII IgG at week five. E. Anti-FVIII IgG incidence, F. Anti- FVIII IgG titers, G. FVIII inhibitor incidence and H. FVIII inhibito- ry activity following re-exposure to FVIII+LPS in E17KO/hMHC mice initially exposed to FVIII or FVIII+Dex and with no evi- dence of anti-FVIII IgG at week five. Some statistical compar- isons could not be carried out because fewer than three mice had evidence of antibodies and/or inhibitors. FVIII: factor VIII; Dex: dexamethasone; IgG: immunoglobulin G; LPS: lipopolysaccharide; ND: not detectable.
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