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

Abstract

Background: Altered levels of Immunoglobulin E (IgE) represent a dysregulation of IgE synthesis and may be seen in a variety of immunological disorders. The object of this review is to summarize the historical and molecular aspects of IgE synthesis and the disorders associated with dysregulation of IgE production.

Methods: 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.

Results: 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.

Conclusion: 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.

Figure 1

Historical aspects of Immunoglobulin E. Charles Richet (A-Credit: Wellcome Library, London: Charles Robert Richet), Paul Ehrlich (B and C-Wellcome Library, London Portrait of P. Ehrlich at work in his laboratory), Teruko and Kimishige Ishizaka (D- Courtesy of the Alan Mason Chesney Medical Archives, Johns Hopkins Medical Institutions), Susumu Tonegawa (E- Courtesy Dr. Susumu Tonegawa) and IgE molecule structure (F).

Figure 2

Factors regulating IgE production.

Figure 3

T-B cell interactions, immune synapse (Prepared for the manuscript by Rahul Krishnaswamy) and IgE class switch recombination (shown in inset).

Figure 4

Cytokine regulation of IgE production.

Figure 5

T cell subsets that have effects on IgE (Refer to text for more details).

Figure 6

Potential consequences of IgE hypogammaglobulinemia.