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Immunoglobulin E in Immunologic Deficiency Diseases. I. RELATION

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Immunoglobulin E in Immunologic Deficiency Diseases. I. RELATION Immunoglobulin E in Immunologic Deficiency Diseases. I. RELATION OF IGE AND IGA TO RESPIRATORY TRACT DISEASE IN ISOLATED IGE DEFICIENCY, IGA DEFICIENCY, AND ATAXIA TELANGIECTASIA Stephen H. Polmar, … , Margaret C. Jost, William D. Terry J Clin Invest. 1972;51(2):326-330. https://doi.org/10.1172/JCI106817. Research Article Serum immunoglobulin E concentration was studied in normal children and adults, in 25 patients with isolated IgA deficiency, and in 44 patients with ataxia telangiectasia using a double antibody radioimmunoassay. The geometric mean IgE level of the normal adult population studied was 105 ng/ml, with a broad 95% interval (5-2045 ng/ml). Individuals with concentrations less than 15 ng/ml were considered to be IgE deficient. IgE deficiency, defined in this way, was observed in 7 of 73 normal adults and was not found to be associated with respiratory tract disease. 80% (35 of 44) of patients with ataxia telangiectasia (AT) were IgE deficient, 66% were IgA deficient, and 57% had combined IgE and IgA deficiencies. Although 45% of the patients with AT had respiratory tract disease, there was no correlation found between IgE deficiency or combined IgE and IgA deficiency and respiratory tract disease in these patients. 11 of 25 individuals with isolated IgA deficiency were also IgE deficient. All 11 patients with both IgA and IgE deficiency were uniformly asymptomatic. However, there was an extremely high incidence (71%) of respiratory tract disease in IgA- deficient individuals who were not IgE deficient. These data fail to support the concept of a protective role for IgE in respiratory tract immunity. The possible role of IgE in the pathogenesis of respiratory tract disease in […] Find the latest version: https://jci.me/106817/pdf Immunoglobulin E in Immunologic Deficiency Diseases I. RELATION OF IGE AND IGA TO RESPIRATORY TRACT DISEASE IN ISOLATED IGE DEFICIENCY, IGA DEFICIENCY, AND ATAXIA TELANGIECTASIA STEPHEN H. POLMAR, THOMAS A. WALDMANN, SUELLEN T. BALESTRA, MARGARET C. JOST, and WILLIAM D. TERRY From the Immunology and Metabolism Branches, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014 A B S T R A C T Serum inmiunoglobulin E concentration association with asthma and other atopic diseases has was studied in normal children and adults, in 25 patients been well established (1-3). The function of IgE in in- with isolated IgA deficiency, and in 44 patients with fectious disease processes is, however, less clear. Chronic ataxia telangiectasia using a double antibody radioim- sinopulmonary disease has been noted in a patient with munoassay. The geometric mean IgE level of the normal isolated IgE deficiency (4) and in a patient with com- adult population studied was 105 ng/ml, with a broad bined IgA and IgE deficiency (5). In addition, there 95% interval (5-2045 ng/ml). Individuals with concen- is an apparent association of respiratory tract disease trations less than 15 ng/ml were considered to be IgE with combined IgA and IgE deficiency in patients with deficient. IgE deficiency, defined in this way, was ob- ataxia telangiectasia (6, 7). These findings have led to served in 7 of 73 normal adults and was not found to be the suggestion that IgE itself or in combination with associated with respiratory tract disease. IgA plays an important role in the protection of respira- 80% (35 of 44) of patients with ataxia telangiectasia tory tract mucosa against infection (5, 6). However, this (AT) were IgE deficient, 66% were IgA deficient, and postulate has recently been called into question by the 57% had combined IgE and IgA deficiencies. Although observation of a healthy IgE-deficient individual (8) 45% of the patients with AT had respiratory tract dis- as well as the absence of IgE deficiency in IgA-deficient ease, there was no correlation found between IgE defi- patients with significant respiratory tract disease (9). ciency or combined IgE and IgA deficiency and respira- The purpose of this study was to determine the serum tory tract disease in these patients. IgE concentrations of normal children and adults, of in- 11 of 25 individuals with isolated IgA deficiency were dividuals with isolated IgA deficiency, and patients with also IgE deficient. All 11 patients with both IgA and ataxia telangiectasia. Our data fail to support the con- IgE deficiency were uniformly asymptomatic. However, cept of a protective role for IgE in the respiratory tract. there was an extremely high incidence (71%0) of On the contrary, the data suggest that the presence of respiratory tract disease in IgA-deficient individuals IgE in individuals with isolated IgA deficiency may be who were not IgE deficient. These data fail to support associated with a high incidence of respiratory tract the concept of a protective role for IgE in respiratory disease. tract immunity. The possible role of IgE in the patho- genesis of respiratory tract disease in IgA-deficient pa- METHODS tients is discussed. Sera. 73 sera were obtained from normal adult blood donors at the National Institutes of Health Blood Bank and INTRODUCTION from laboratory personnel (age range 21-60 yr). No at- tempt was made to exclude individuals with a history of al- The role of immunoglobulin E (IgE) in the mediation lergy. Sera of 71 normal nonallergic infants and children, of immediate hypersensitivity reactions in man and its ranging in age from birth to 15 yr, were obtained from children studied at the National Institutes of Health or Received for publication 13 July 1971 and in revised form provided by Doctors H. Lischner, L. Robinson, and A. B. 26 September 1971. Minnefor. Sera from 44 patients with ataxia telangiectasia 326 The Journal of Clinical Investigation Volume 51 1972 TABLE I Serum IgE Concentration (nanograms/milliliter) in Normal and Immune Deficient Individuals 95% Number Mean interval P* % <15 Normal adults 73 105 5-2045 - 10 Isolated IgE deficiency 7 8 5-14 100 Isolated IgA deficiency 25 35 1-1396 <0.02 44 (28)1 Ataxia telangiectasia (total) 44 12 1-122 <0.001 80 Ataxia telangiectasia with IgA present 15 19§ 2-174 <0.001 66 Ataxia telangiectasia with IgA deficiency 29 10§ 1-93 <0.001 86 * Geometric means of patient groups are compared with that of the normal adult population using Student's t test. $ The value in parenthesis is the percentage of IgE deficiency among 18 independently ascertained IgA deficient individuals. § The difference between these mean values is not significant, P > 0.05. (AT),' 25 patients with isolated IgA deficiency, and 3 pa- Radioimmunoassay of serum immunoglobulin E. Serum tients with known isolated IgE deficiency were obtained IgE was measured by a double antibody method employing from Doctors A. J. Ammann, H. N. Claman, M. D. Cooper, specific rabbit anti-IgE (P.S.) and 'I-labeled IgE (N.D.) P. Fireman, D. Frommel, R. A. Good, A. Lawton, D. A. (14, 15). Standard inhibition curves were obtained by the Levy, H. A. Lischner, and M. L. Schulkind, as well as from addition of known amounts of purified unlabeled IgE our own patient population. All sera were stored frozen (N.D.) or IgE (P.S.). A standard curve was constructed at - 200C before study. Information concerning exact diag- for each assay by plotting the logit of the percentage of nosis, clinical picture, quantitative serum immunoglobulin, specific counts bound vs. logio nanograms of IgE added to and delayed hypersensitivity studies was also collected and the reaction mixture (16). These curves were linear from tabulated for each patient. 0.2 to 28 ng. IgE concentration of unknown serum samples Quantitation of serum immunoglobulins with the excep- was calculated from the coordinates of the least squares tion of IgE. The concentrations of immunoglobulins G, A, regression equation of the standard inhibition curve. The M, and D were determined by single radial diffusion in average standard deviation of duplicate determinations per- agar (10, 11). formed on different days was 2.6%. Specificity of the assay Purified IgE myeloma proteins. A purified preparation for IgE was checked through the study of purified IgG of the IgE myeloma protein from patient N.D., was kindly and IgA myeloma proteins as well as sera from patients provided by Doctors S. G. 0. Johansson and H. Bennich. with IgG, IgA, and IgD myeloma, Waldenstrom's macro- Purified IgE myeloma protein from patient P. S., was ob- globulinemia, and sex-linked recessive agammaglobulinemia. tained from plasma (kindly provided by Dr. 0. Ross Statistical methods. Serum immunoglobulin concentrations McIntyre) by elution from diethylaminoethyl-cellulose are not distributed in a Gaussian manner (17, 18). The (Whatman DE-52) at 0.025 M Tris-HCI, pH 8.0, and fur- logarithm to the base 10 of the immunoglobulin concentra- ther purified by gel filtration on Sephadex G-200 columns. tion is, however, often normally distributed (18). For this Protein concentrations of these purified preparations were reason the geometric mean rather than the arithmetic mean determined by absorbance at 280 nm. E9S = 15 was assumed was used to estimate the median values for a given- im- for both the P.S. and N.D. myeloma proteins. munoglobulin in a population, and the log1o of the immuno- Antisera. Antisera to IgE (P.S.) were produced in rab- globulin concentration was used in all statistical tests. Statis- bits. Copolymers containing bovine serum albumin, fetal tical analyses were performed by Student's t test, Fisher's bovine serum, IgG, IgA, IgM, P.S. light chains, and agam- exact test for 2 X 2 contingency tables, and least squares re- maglobulinemic plasma, prepared by ethyl chloroformate gression analysis using standard methods (19). insolubilization (12), were used to absorb the antisera and render them specific for IgE. Specificity of the antisera was confirmed by Ouchterlony double diffusion tests.
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