The present invention relates to the treatment of IgE-mediated disease. The inventors hypothesized that formation of immune complexes between Omalizumab and IgE might be responsible for some of the adverse reactions observed in highly atopic patients (i.e. patients with a history of anaphylaxis and/or high IgE titers). Immune complexes can induce inflammation through activation of Fc gamma receptors (FcγRs) and/or the complement cascade. They identified that Omalizumab:hIgE immune complexes activate human FcγRs in vitro. Moreover, similarly to some of the reported side effects observed in human, Omalizumab:hIgE immune complexes can induce anaphylaxis when injected in mice expressing human FcγRs. Using publicly available omalizumab VH and VL sequences, they cloned and produced two mutant versions of omalizumab in which residues in the Fc portion of the Ab were mutated. These variants did not induce anaphylaxis when injected into mice expressing human FcγRs and could be thus used for the treatment of IgE-mediated disease. Thus invention relates to a recombinant immunoglobulin heavy chain protein which comprises at least one mutation in the Fc portion and recombinant antibody comprising said heavy chain protein.