Seronegative antibody-mediated irAEs have also been described in other irAEs explained by the abnormal release of cytokines and chemokines, which decrease the function of Tregs and the systemic and organ-specific inflammation or by the direct off-target effect of ICIs on cells bearing the targeted checkpoint ligand, as in the case of hypophysitis after anti-CTLA-4 treatment [22]. The gene discussed is CTLA4; the disease is hypophysitis.