Fig. 2

a Laboratory characteristics in CSU. In the classic allergic pathway, allergy sensitization and provocation by exogenous allergens and subsequent mast cell granulation and allergen-specific Th2 activation result in an increase in allergen-specific IgE (SIgE), serum total IgE (Total IgE), blood eosinophil fraction and serum eosinophil cationic protein. However, the immunopathogenesis of CSU bypasses the exogenous allergen-IgE-FcεRI pathway, and the representative allergy laboratory tests were possibly all negative. b Revised action mechanisms of Histobulin™ in CSU. The immunopathogenesis of CSU was revised step by step as autoantigen-specific IgE and autoantigen binding (step 1a), the IgG or IgM autoantibody binding to IgE (step 1b), binding of autoantigen-IgE complex or anti-IgE IgG/IgM antibody-IgE complex to FcεR1 (step 2a), binding of anti-FcεR1 autoantibody to FcεR1 (step 2b), histamine release with mast cell degranulation (step 3) and high level of histamine and binding to histamine receptor which leads to clinical manifestations of allergy (step 4). Histobulin™ has the effects of histaminopexy and induces antihistamine antibodies. Histobulin™ possibly decreases serum histamine levels at step 4. Histobulin™ inhibits antigen-induced histamine release from human peripheral blood basophils at step 3. Histobulin™ decreases specific IgE clinically and affects step 1a (IgE antibody to autoantigens). The main constituent of Histobulin™ is immunoglobulin, and IVIG effects were possibly expected in Histobulin™. Histobulin™ may be effective in step 1b (IgG and IgM autoantibody to IgE) and step 2b and step 2b (autoantibody to FcεR1)