Anti-immunoglobulin E for the treatment of allergic disease

Abstract Context.—The diagnostic algorithm for human allergic disease involves confirmation of sensitization by detection of allergen-specific immunoglobulin E (IgE) antibody in individuals suspected of having allergic disease because of a history of allergic symptoms after known allergen exposure. Previous studies showed wide disparity among clinically reported allergen-specific IgE levels from different serologic assays. Objective.—To validate the relative analytic performance (sensitivity, interassay reproducibility, linearity/parallelism, intermethod agreement) of clinically used total and allergen-specific IgE assays by using College of American Pathologists' Diagnostic Allergy “SE” Proficiency Survey data. Design.—Data from 2 SE survey cycles were used to assess relative analytic performance of the ImmunoCAP (Phadia), Immulite (Siemens Healthcare-Diagnostics), and HYTEC 288 (HYCOR-Agilent Technologies) total and allergen-specific IgE assays. In each cycle, 2 recalcified plasma pools from atopic donors were diluted twice with IgE-negative serum and evaluated in approximately 200 federally certified clinical laboratories for total IgE and IgE antibody to 5 allergen specificities. Statistical analysis evaluated analytic sensitivity, linearity, reproducibility, and intermethod agreement. Results.—Interlaboratory intramethod, intermethod, and interdilution agreement of all 6 clinically used total serum IgE assays were excellent, with coefficients of variation (CVs) below 15%. Interlaboratory intramethod, and interdilution agreement of 3 clinically used allergen-specific IgE assays were also excellent with CVs below 15%. However, intermethod CVs identified between-assay disagreement greater than 20% in 80% of allergen-specific IgE measurements. Allergen reagents and patients' immune response heterogeneity are suggested probable causes. Conclusions.—Clinical total and allergen-specific IgE assays display excellent analytic sensitivity, precision, reproducibility, and linearity. Marked variability in quantitative estimates of allergen-specific IgE from clinically used automated immunoassays is a concern that may be ameliorated with component allergen use.

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Fibrin(ogen) Mechanistically Contributes to Atopic Dermatitis Pathogenesis and Allergic Sensitization

Blood ◽

10.1182/blood-2021-153782 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2097-2097

Author(s):

Alyssa Filuta ◽

Peter K Amezcua ◽

Brandy Ruff ◽

Hua He ◽

Lisa J Martin ◽

...

Keyword(s):

Atopic Dermatitis ◽

Disease Severity ◽

Allergic Disease ◽

Immunoglobulin E ◽

Critical Role ◽

Allergic Sensitization ◽

Skin Barrier Function ◽

P Value ◽

Increased Risk ◽

The Impact

Abstract Adults with atopic dermatitis (AD) have an increased risk for thromboembolic events. While coagulation is critical for almost all healing responses, dysregulated clotting and fibrin(ogen) deposition lead to inflammation that exacerbates tissue damage and impairs tissue repair. While plasma fibrin(ogen) has been associated with established asthma, fibrin(ogen)'s mechanistic role in AD pathogenesis and allergic sensitization has not been investigated. Here we show that fibrinogen plays a critical role in a murine model atopic dermatitis pathogenesis by markedly attenuating disease severity, barrier dysfunction, and allergic sensitization. To determine if fibrinogen impacts AD pathogenesis, we used mice with complete fibrinogen deficiency (Fib -/-), partial deficiency (Fib +/-), and wildtype controls (Fib WT) in our established model of AD. This model uses repeated cutaneous allergen sensitization with heat-killed Aspergillus fumigatus (Asp) extract. Notably, Fib +/- mice produce approximately half as much fibrinogen as Fib WT mice. After each patch and at sacrifice each mouse underwent an objective disease severity assessment as well as transepidermal water loss (TEWL) measurements to assess skin barrier function. Our results show that complete and partial fibrinogen deficiency abrogated AD development. We found that Fib -/-and Fib +/- mice had markedly attenuated TEWL (P-value <0.0001) and disease severity (P-value <0.0001) compared with controls (Figure 1). In addition, we found that the TEWL and disease severity in Fib -/- and Fib +/- were comparable to unchallenged controls. There was also no difference in either outcome between Fib -/- and Fib +/- mice within the experimental group. Lastly, none of the Fib -/- and Fib +/- mice developed spontaneous bleeding. Next, to elucidate the impact of fibrinogen on allergic sensitization we measured plasma allergen specific immunoglobulin E (sIgE) to Asp in all mice in our AD model at sacrifice. We found that Fib -/- and Fib +/- mice had significantly lower Asp sIgE compared with controls (p-value <0.0001 and 0.0002, respectively; Figure 2). In addition, we found that the amount of sIgE to Asp produced was comparable between Fib -/- and Fib +/- mice as well as with unchallenged controls. Thus, our findings suggest that fibrin(ogen) plays a critical mechanistic role in driving AD development and allergic sensitization. While fibrinogen's role in established allergic disease has been shown, these novel findings suggest a critical role for fibrinogen in allergic disease pathogenesis which may allow for additional therapeutic targets to treat atopic dermatitis and other allergic diseases. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Study of total Immunoglobulin E and Eosinophil count in allergic disease

Baghdad Science Journal ◽

10.21123/bsj.2016.13.2.0298 ◽

2016 ◽

Vol 13 (2) ◽

pp. 298-304

Keyword(s):

Allergic Disease ◽

Eosinophil Count ◽

Immunoglobulin E ◽

Total Immunoglobulin

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Analysis of total immunoglobulin E and specific immunoglobulin E of 3,721 patients with allergic disease

Biomedical Reports ◽

10.3892/br.2015.455 ◽

2015 ◽

Vol 3 (4) ◽

pp. 573-577 ◽

Cited By ~ 10

Author(s):

MAN-LI CHANG ◽

CAN CUI ◽

YAN-HONG LIU ◽

LI-CHUN PEI ◽

BING SHAO

Keyword(s):

Allergic Disease ◽

Immunoglobulin E ◽

Specific Immunoglobulin E ◽

Specific Immunoglobulin ◽

Total Immunoglobulin

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Diagnosing Allergic Diseases in Children

Archives of Pathology & Laboratory Medicine ◽

10.5858/2004-128-1028-dadic ◽

2004 ◽

Vol 128 (9) ◽

pp. 1028-1031

Author(s):

Henry A. Homburger

Keyword(s):

Allergic Disease ◽

Immunoglobulin E ◽

Signs And Symptoms ◽

Allergic Diseases ◽

Definitive Diagnosis ◽

Management Options ◽

Presumptive Diagnosis ◽

Laboratory Services ◽

Minimum Number ◽

Antibody Tests

Abstract In the environment of managed care, children with allergic diseases are increasingly likely to be evaluated by nonallergist physicians. While the presumptive diagnosis of an allergic disease can often be suspected on clinical grounds, signs and symptoms are not reliable for establishing a definitive diagnosis or for deciding on management options. This article discusses the use of immunoglobulin E antibody tests to classify children with allergic symptoms. The information is intended for pathologists who offer consultative laboratory services to nonallergist physicians. Emphasis is placed on defining the minimum number of tests necessary to identify allergic children at different ages.

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Efficacy of hyposensitization in feline allergic diseases based upon results of in vitro testing for allergen-specific immunoglobulin E

Journal of the American Animal Hospital Association ◽

10.5326/15473317-33-3-282 ◽

1997 ◽

Vol 33 (3) ◽

pp. 282-288 ◽

Cited By ~ 29

Author(s):

RE Halliwell

Keyword(s):

Allergic Disease ◽

Immunoglobulin E ◽

Clinical Signs ◽

Allergic Diseases ◽

Dietary Change ◽

In Vitro Tests ◽

Similar Response ◽

Specific Immunoglobulin E ◽

Specific Immunoglobulin

A survey was undertaken to evaluate the responses to hyposensitization in cats for which a diagnosis of allergic disease was made by assessment of clinical signs and evaluation of allergen-specific immunoglobulin E (IgE) using the radioallergosorbent test (RAST). Eighty-one cases were available for analysis. In 39 cases, a dietary change resulted in some subjective improvement, which usually was minimal; however, some cases had significant improvement. In 75.3% of cases, an improvement of at least 50% was noted and ascribed to a combination of immunotherapy and dietary change, when implemented. The response of the 42 cases in which immunotherapy alone was used or where there was no response to dietary change was broadly similar. Response of the specific dermatological conditions ranged from 93.6% in the case of linear granuloma to 60% in cases where self-induced hair loss was evident. Response also was good in cases of presumed allergic asthma (86.1% improvement) and suspected allergic otitis externa (62.6% improvement). In nine patients, the hyposensitization was discontinued due to lack of response. The results suggest that confirmation of a suspected diagnosis of allergic disease in cats by means of in vitro tests and subsequent therapy with hyposensitization should be a major consideration in feline practice.

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