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We recently published a model (1) that proposes a molecular basis for the anti-inflammatory properties of sialylated IgG Fc (sFc), resulting from its observed shift in receptor specificity from FcγRs to dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)/CD23, a consequence of changes to the structure of the CH2 domain that we observe upon sialylation. However, Crispin et al. (2) report a crystal structure of a sFc that resembles that of an earlier reported structure, 1H3Y (3), which carries a nonsialylated Fc. The basis for this discrepancy likely results from the fact that both crystal structures of sialylated and nonsialylated Fcs have been obtained under similar but nonphysiological conditions (>2 M sodium chloride, …

Reply to Crispin et al.: Molecular model that accounts for the biological and physical properties of sialylated Fc