Human factor VIII and N-linked carbohydrates. The left panel shows the secondary structure of factor VIII and its domains. Indicated are the putative twenty-five N-linked carbohydrates sites and a typical N-linked carbohydrate structure found on FVIII with terminal N-acetylneuraminic acid (Neu5Ac) decorations. The middle panel shows an N-linked carbohydrate structure decorated with terminal nonhuman αGal moieties. The second-generation rFVIII expressed in BHK cells has a heightened amount of nonhuman αGal moieties compared with the third-generation rFVIII expressed in CHO cells (right panel). The non-human form of sialic acid decoration Neu5Gc, only indicated in the CHO-expressed rFVIII, is likely expressed in the BHK-rFVIII. Increasing αGal moieties likely contributes to the immunogenicity of rFVIII. GlcNAc, N-acetylglucosamine. Professional illustration by Somersault 18:24.