The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies

J Clin Invest. 1976 Aug;58(2):408-20. doi: 10.1172/JCI108485.


IgE antibodies are usually thought to induce only immediate skin reactions. We have shown that the intradermal injection of a number of different allergens can produce a prolonged inflammatory reaction after the immediate wheal and flare in most sensitive subjects. This late inflammatory response occurs 6-12 h after challenge and is characterized by diffuse edema, erythema, pruritus, and heat. Both immediate and late responses can also be seen after passive sensitization of skin sites in nonatopic subjects. That IgE is involved in inducing the reaction was shown by the abolition of both immediate and late responses by passive transfer tests in the following experiments: (a) heating atopic serum at 56degreesC for 4 h, (b) removing IgE from the atopic serum by a solid phase anti-IgE immunoabsorbent, and (c) competitively inhibiting the binding of IgE antibodies to cells by an IgE myeloma protein. In addition, both responses were induced by affinity chromatography-purified IgE antibody, followed by antigenic challenge. Very similar lesions could also be induced by intradermal injection of Compound 48/80, thus suggesting a central role in the reaction for the mast cell or basophil. Histologically, the late phase is characterized by edema and a mixed cellular infiltration, predominantly lymphocytic but also containing eosinophils, neutrophils and basophils. Direct immunofluorescent staining did not show deposition of immunoglobulins or complement components, except IgM in 2 of 15 and C3 in 1 of 15 patients. This finding indicates that the late phase does not depend on the deposition of immune complexes. The results of the study suggest that IgE-allergen interaction on the surfaces of mast cells or on infiltrating basophils causes both immediate and late cutaneous responses.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Basophils / immunology
  • Clinical Trials as Topic
  • Complement C3 / analysis
  • Humans
  • Hypersensitivity, Immediate / immunology*
  • Hypersensitivity, Immediate / pathology
  • Hypersensitivity, Immediate / physiopathology
  • Immunization, Passive
  • Immunoglobulin E* / metabolism
  • Immunoglobulin M / analysis
  • Mast Cells / immunology
  • Skin / pathology
  • Skin Tests*
  • p-Methoxy-N-methylphenethylamine


  • Complement C3
  • Immunoglobulin M
  • Immunoglobulin E
  • p-Methoxy-N-methylphenethylamine