Regulation and dysregulation of immunoglobulin E: a molecular and clinical perspective

Articles published in Medline/PubMed were searched with the keyword Immunoglobulin E and specific terms such as class switch recombination, deficiency and/or specific disease conditions (atopy, neoplasia, renal disease, myeloma, etc.). The selected papers included reviews, case reports, retrospective reviews and molecular mechanisms. Studies involving both sexes and all ages were included in the analysis.Both very low and elevated levels of IgE may be seen in clinical practice. Major advancements have been made in our understanding of the molecular basis of IgE class switching including roles for T cells, cytokines and T regulatory (or Treg) cells in this process. Dysregulation of this process may result in either elevated IgE levels or IgE deficiency.Evaluation of a patient with elevated IgE must involve a detailed differential diagnosis and consideration of various immunological and non-immunological disorders. The use of appropriate tests will allow the correct diagnosis to be made. This can often assist in the development of tailored treatments.Immunoglobulin E has traditionally been associated with atopic disease and systemic anaphylaxis. However, its role in host defense, parasitic infection and immune surveillance suggest many other potential functions. The initial description of anaphylaxis was made by Portier and Richet in 1902 which led to Richet receiving the Nobel Prize for medicine in 1913 (Figure 1A). The mast cell was first described by Paul Ehrlich while experimenting with Aniline dyes as a medical student in 1878 (Figure 1B and 1C); he was awarded the Nobel Prize for his therapeutic discoveries in Medicine in 1908. The discovery of IgE by the Ishizakas (Figure 1D) in 1966 was a major advancement. Further understanding of IgE immunobiology was made possible by the description of class switch recombination (discussed later) by Susumu Tonegawa (Figure 1E), a Japanese scientist working in the United States. For this, he was awarded the Nobel Prize in Me