Selective IgE deficiency, immune dysregulation, and autoimmunity.

Selective IgE deficiency (IgED) is currently defined as a significant decrease in serum levels of IgE (!2 kIU/L) in a patient whose other immunoglobulin levels are normal. There are no published large-scale epidemiological studies regarding the prevalence of and clinical features of IgED. In the population-based case–control study, we investigated clinical and laboratory characteristics of patients with IgED. Case samples were drawn from all subjects (n " 18487), with serum total IgE measurement during 2012 at Leumit Health Care Services (Israel) and had serum total IgE of !2 kIU/L. The control group was randomly sampled from the remaining 18,261 subjects with a case–control ratio of four controls for each case (1:4). Comorbid diseases were identified by specific International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes given by the corresponding board-certificated physicians. Two hundred twenty-six subjects showed serum total IgE levels of !2 kIU/L; 68 (30.9%) were between the ages of 4 and 12 years (children) and 250 (69.1%) were !12 years old (adults). Matched control groups were selected for each age group. The children group was characterized by higher prevalence of asthma and hyperreactive airways disease; and both children and adult groups had significantly higher prevalence of chronic sinusitis, otitis media, autoimmune, and oncological diseases than their respective controls. Undetectable serum total IgE may serve as a marker of immune dysregulation and autoimmunity. (Allergy Asthma Proc 35:e27–e33, 2014; doi: 10.2500/aap.2014.35.3734) A the discovery of IgE, there was great success in understanding its role in immediate hypersensitivity, host defense, parasitic infection, and immune surveillance; however, the pathophysiological consequences of IgE hypogammaglobulinemia remain understudied. Compared with the major circulating immunoglobulins (IgG, IgA, and IgM), IgE is the least abundant of the human immunoglobulin classes and was, accordingly, the last to be discovered in the late 1960s. The concentration of IgE in normal human sera is between 10 and 400 ng/mL, and its half-life in the circulation, is estimated at 2–2.5 days, whereas serum IgG has a half-life of #3 weeks. IgE is best known for its pathological effects in allergic diseases and the beneficial role of IgE in host defense against parasitic infections, in particular, against helminth infections. There have been few studies on patients with a low or undetectable serum total IgE. Normal levels of IgE are highly variable within the population. Selective IgE deficiency (IgED) is currently defined as a significant decrease in serum levels of IgE (!2 kIU/L) in a patient whose other immunoglobulin levels are normal or diminished (mixed IgED). Mainly, it is a laboratory finding and the vast majority of affected individuals are asymptomatic. There are no published large-scale epidemiological studies regarding the prevalence of IgE hypogammaglobulinemia and IgED. In this population-based case–control study, we attempted to investigate clinical and laboratory characteristics of patients with IgED. MATERIALS AND METHODS