Figure 2.
Patient anti-FVIII drug antibodies bind preferentially to a subset of FVIII disulfide-bonded states. (A) Ribbon representation of the AlphaFold structure of human FVIII lacking the unstructured B domain. The domains to which a panel of 5 patient-derived anti-FVIII drug antibodies bind (BOIIB2, KM41, LE2E9, KM33, and BO2C11) are shown. The residues that encompass the epitopes for the antibodies are shown as dots (see Table 1 for residue numbers) and the disulfide bond cysteines as yellow spheres. (B) Incidence of unformed disulfide bonds in the bound vs unbound FVIII (n = 3 experiments). The mean values for the starting (total) FVIII are shown as green crosses. Errors are mean ± SD. The patient anti-FVIII antibodies bound preferentially to FVIII covalent states in which 3 of the 8 disulfides are significantly more unformed (∗P < .05; ∗∗P < .01; ∗∗∗P < .001).

Patient anti-FVIII drug antibodies bind preferentially to a subset of FVIII disulfide-bonded states. (A) Ribbon representation of the AlphaFold structure of human FVIII lacking the unstructured B domain. The domains to which a panel of 5 patient-derived anti-FVIII drug antibodies bind (BOIIB2, KM41, LE2E9, KM33, and BO2C11) are shown. The residues that encompass the epitopes for the antibodies are shown as dots (see Table 1 for residue numbers) and the disulfide bond cysteines as yellow spheres. (B) Incidence of unformed disulfide bonds in the bound vs unbound FVIII (n = 3 experiments). The mean values for the starting (total) FVIII are shown as green crosses. Errors are mean ± SD. The patient anti-FVIII antibodies bound preferentially to FVIII covalent states in which 3 of the 8 disulfides are significantly more unformed (∗P < .05; ∗∗P < .01; ∗∗∗P < .001).

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