Answer:
Deficiency or low IgE is defined by an IgE concentration of less than 2.5 IU/ml thus the level mentioned would meet this definition. There is no specific immunodeficiency identified by isolated IgE deficiency and selective IgE deficiency is not included in the classification of primary immunodeficiency diseases (1). The frequency of isolated IgE deficiency varies according to the population studied, ranging from 0.8 to 9.7%; the majority of studies suggest a prevalence of 1-2.6% (2). Despite the absence of a specific disease or syndrome attributed to deficient IgE, there is an association with nonallergic airway symptoms, autoimmune disease, immunodeficieny and possibly an increase in cancer (3-4). There are associations with humoral immunodeficiencies including IgA, IgG4 and IgG deficiency. In the absence of symptoms, I do not feel there is a necessity in testing for humoral immunodeficiency.
In summary, there is an association of IgE deficiency and autoimmunity, but I am not aware of an association with Crohn disease. There is an association with IgE deficiency and increased respiratory symptoms and IgA deficiency. I would assess for chronic sinusitis in light of symptoms of nasal congestion with fiberoptic rhinolaryngoscopy or sinus imaging. If no significant findings are noted, I would not recommend any further immunologic testing. I am not aware of any relationship with anti-TNF or mercaptopurine therapy and IgE deficiency.
1. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015.
Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Puck JM, Sullivan KE, Tang ML, Franco JL, Gaspar HB
J Clin Immunol. 2015;35(8):696. Epub 2015 Oct 19.
We report the updated classification of primary immunodeficiencies compiled by the Primary Immunodeficiency Expert Committee (PID EC) of the International Union of Immunological Societies (IUIS). In the two years since the previous version, 34 new gene defects are reported in this updated version. For each disorder, the key clinical and laboratory features are provided. In this new version we continue to see the increasing overlap between immunodeficiency, as manifested by infection and/or malignancy, and immune dysregulation, as manifested by auto-inflammation, auto-immunity, and/or allergy. There is also an increased number of genetic defects that lead to susceptibility to specific organisms which reflects the finely tuned nature of immune defense systems. This classification is the most up to date catalogue of all known and published primary immunodeficiencies and acts as a current reference of the knowledge of these conditions and is an important aid for the genetic and molecular diagnosis of patients with these rare diseases.
2. Clinical manifestations of IgE hypogammaglobulinemia.
Smith JK, Krishnaswamy GH, Dykes R, Reynolds S, Berk SL
Ann Allergy Asthma Immunol. 1997;78(3):313.
BACKGROUND: Although IgE has been shown to play a role in the expulsion of intestinal parasites in experimental animals, its overall contribution to host defense in humans remains a subject of controversy. In order to clarify the potential role of IgE in host defense, we have studied the clinical characteristics of patient with serum IgE levels of<2.5 IU/mL, using patients with normal or elevated IgE levels as controls.
OBJECTIVE: To determine the clinical characteristics of IgE deficiency.
METHODS: Serum IgE levels were measured in 420 adult patients seen in our Allergy-Immunology Clinic over a period extending from January, 1990 to March, 1996. All subjects were examined by one of the authors (JKS or GHK) using a standardized history and physical examination form. Patients with IgE levels of<2.5 IU/mL also had measurements of serum IgG, IgG subclasses, IgA and IgM. All IgE-deficient patients and 73% of those with normal to elevated IgE levels underwent RAST and/or skin testing for Type I hypersensitivity, and, where clinically indicated, had serum drawn for autoimmune serologic profiles. Infectious complications were documented by culture. The American Rheumatology Association criteria were used to establish a diagnosis of autoimmune disease.
RESULTS: Forty-four patients were found to have IgE levels of<2.5 IU/mL; 57% of these had depressed serum levels of other immunoglobulins, and 43% had isolated IgE deficiencies. Respiratory symptoms were equally common in IgE-deficient patients and in patients with normal to elevated IgE levels. IgE-deficient patients, however, were more likely to complain of arthralgias (P<.0001), chronic fatigue (P<.0001), and symptoms suggestive of airway infection (P = .0119). Compared with controls, patients with IgE deficiency had a higher prevalence of autoimmune disease (46% versus 15%) (P<.0001) and nonallergic reactive airway disease (73% versus 20%) (P<.0001). There was no difference in the prevalence of these disease in patients with selective IgE deficiency as compared with those with IgE deficiency complicated by deficits in other immunoglobulin classes. IgE-deficient patients with multiple immunoglobulin deficiencies, however, were more likely to have serious infection involving both the upper and lower respiratory tract than those with isolated IgE deficiency.
CONCLUSIONS: IgE-deficient patients have an increased prevalence of multiple immunoglobulin deficits, autoimmune disease, and nonallergic reactive airway disease when compared with a clinic population of patients with normal to elevated IgE levels.
3. Increased malignancy incidence in IgE deficient patients not due to concomitant Common Variable Immunodeficiency.
Ferastraoaru D, Gross R, Rosenstreich D
Ann Allergy Asthma Immunol. 2017;119(3):267. Epub 2017 Aug 1.
BACKGROUND: Immunoglobulin E (IgE) deficiency (<2.5 kU/L) has unclear clinical significance. Very little is known about the clinical characteristics of IgE deficiency in patients with Common Variable Immunodeficiency (CVID).
OBJECTIVE: To evaluate the clinical and laboratory differences between patients with IgE deficiency and those with non-IgE deficiency with and without CVID diagnosis.
METHODS: This is a retrospective study of adult patients who had total serum IgE levels measured at our facility from 2010 through 2015. Patients with IgE levels lower than 2.5 kU/L composed the IgE deficiency group. We used Clinical Looking Glass software to identify laboratory results and comorbid conditions including CVID and malignancy.
RESULTS: The IgE levels were measured in 2,339 patients and 63 (2.7%) had IgE deficiency. Of those with IgE deficiency, 14 of 63 (22%) had CVID diagnosis compared with only 62 of 2,276 patients(2.7%) with non-IgE deficiency and CVID. A significantly higher rate of prior malignancy was found in patients with IgE deficiency (21 of 63, 33%) compared with those with non-IgE deficiency (197 of 2,276, 8.7%; P = .001; odds ratio 5.51, 95% confidence interval 3.07-9.88). Six of 14 patients with CVID and IgE deficiency (43%) had a prior malignancy diagnosis compared with 8 of 62 patients (13%) with CVID and non-IgE deficiency (P = .009; odds ratio 10.65, 95% confidence interval 1.79-63.19). In addition to the higher rate of malignancy, patients with CVID and IgE deficiency did not have more severe disease than those with CVID and non-IgE deficiency.
CONCLUSION: The rate of prior malignancy is significantly higher in patients with IgE deficiency than in those without IgE deficiency. Similarly, patients with CVID and IgE deficiency have a higher frequency of prior malignancy than those with CVID and non-IgE deficiency. However, patients with IgE deficiency have higher frequency of malignancy than patients with normal IgE levels even in the absence of CVID.
4. Selective IgE deficiency, immune dysregulation, and autoimmunity.
Magen E, Schlesinger M, David M, Ben-Zion I, Vardy D
Allergy Asthma Proc. 2014;35(2):e27.
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.
I hope this information is of help to you and your practice.
All my best.
Dennis K. Ledford, MD, FAAAAI