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Immune responses to human factor IX in haemophilia B mice of different genetic backgrounds are distinct and modified by TLR4 by B. K. Sack; X. Wang; A. Sherman; G. L. Rogers; D. M. Markusic is a Medicine article available to read on EtoBox.

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## Summary Our laboratory develops protocols to prevent or reverse ongoing anti‐hFIX IgG inhibitors in haemophilia B mice with a __F9__ gene deletion on BALB/c and C3H/HeJ backgrounds. C3H/HeJ __F9__^−/Y^ mice develop high titre anti‐hFIX IgG1 inhibitors and anaphylaxis, whereas most BALB/c __F9__^−/Y^ mice have mild anti‐hFIX IgG1 inhibitors and no anaphylaxis. Our aim was to determine if hFIX‐specific B‐ and T‐cell responses in BALB/c and C3H/HeJ __F9__^−/Y^ mice trigger the difference in anti‐hFIX immune responses. BALB/c and C3H/HeJ __F9__^−/Y^ mice were challenged weekly with recombinant hFIX protein. Humoral immune responses were determined by IgG1 and IgG2a anti‐hFIX ELISA, Bethesda assay for inhibitors and B‐cell ELISpot on bone marrow and spleen cells. T‐cell studies measured the T~H~1 (IFN‐γ) and T~H~2 (IL‐4) cytokine responses in splenocytes at the mRNA and protein level in response to hFIX protein. Antibody responses were also measured in C3H/HeJ/OuJ __F9__^−/Y^ mice with restored toll‐like receptor 4 (TLR4) function. BALB/c __F9__^−/Y^ mice have a T~H~2 skewed response and a reduction in anti‐hFIX secreting plasma cells in the bone marrow. Independent antigen challenge

Who reads Immune responses to human factor IX in haemophilia B mice of different genetic backgrounds are distinct and modified by TLR4?

Author

B. K. Sack; X. Wang; A. Sherman; G. L. Rogers; D. M. Markusic

Publisher

Wiley

Published

2014

Language

EN

Field

Medicine (Health Sciences)