C4B and hyperimmunoglobulinemia D with periodic fever: Without suitable methods to assess both the potential benefits and immunopathology of antibody isotypes/subtypes as therapeutics (e.g. IgE anaphylaxis, IgA nephropathy, IgM rheumatoid factor, Hyper-IgD syndrome), it may be decades before CH isotype swapping are adopted as the next generation of antibody therapeutics.