Together with our observations, the data suggest that the generation of a novel FVIII therapeutic compromised in its capability to interact with DCs upon the removal of selected N-glycosylation sites ...may be a novel strategy to produce a hemostatically proficient drug with potentially reduced immunogenicity in patients with hemophilia A. We thank Joelle Treton (INSERM U662, Hospital Saint-Louis, Paris, France) for providing us with blood from healthy MHC-matched donors. mAb 77IP52H7 and Factane were gifts from LFB.
Background TH 17 cells play a critical role in the pathogenesis of several autoimmune and allergic diseases. Intravenous immunoglobulin (IVIg), a therapeutic preparation of polyclonal IgG that is ...increasingly used in the treatment of diverse autoimmune and allergic diseases, might target TH 17 cells to exert therapeutic effects. Objective We sought to examine whether IVIg interferes with the development and function of human TH 17 cells. Methods TH 17 cells were differentiated from naive human CD4+ T cells in the presence of TGF-β and IL-21. TH 17 cells were amplified by stimulating memory CD4+ T cells in the presence of IL-1β and IL-6. The effect of IVIg was examined on the differentiation and amplification of TH 17 cells, expression of the TH 17 lineage-specific transcription factor retinoic acid-related orphan receptor C, secretion of TH 17 effector cytokines, and phosphorylation of signal transducer and activator of transcription 3, a transcription factor that plays an important role in TH 17 cell development and function. Results IVIg inhibits the differentiation and amplification of human TH 17 cells, as well as the production of their effector cytokines IL-17A, IL-17F, IL-21, and CCL20. The inhibitory effects of IVIg on TH 17 cells are F(ab′)2 dependent and involve interference with the expression of retinoic acid-related orphan receptor C and activation of signal transducer and activator of transcription 3. Also, IVIg significantly enhanced forkhead box protein 3–positive regulatory T cells among the memory CD4+ T cells. Conclusion These results reveal a novel mechanism of action of IVIg in achieving a therapeutic effect in autoimmune and allergic diseases, in which TH 17 cells play a key modulatory role in sustaining the chronic inflammatory response. Our results also suggest a reciprocal regulation of TH 17 and regulatory T-cell populations by IVIg.
Conclusions Epicutaneous exposure to pdFVIII of hemophilic mice sensitized to FVIII, reduces the immune response to therapeutic FVIII during replacement therapy.
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