Observation of Heavy-Chain C-Terminal Des-GK Truncation in Recombinant and Human Endogenous IgG4.

Therapeutic IgG mAbs have shown presence of three variations of their heavy chain C-termini, including the unprocessed C-terminal lysine, the processed C-terminal lysine, and C-terminal amidation. These variants are also present in endogenous human IgGs, although the level of unprocessed C-terminal lysine is very low. Here we report a new heavy-chain C-terminal variant, i.e., the des-GK truncation, which exists in both recombinant and endogenous human IgG4. The des-GK truncation was found in negligible amount in IgG1, IgG2 and IgG3 subclasses. Observation of a significant level of heavy-chain C-terminal des-GK truncation in endogenous human IgG4 suggests that low level of this variant present in therapeutic IgG4 is unlikely to be a safety concern.