Use of recombinant human interferon gamma to enhance neutrophil chemotactic responses in Job syndrome of hyperimmunoglobulinemia E and recurrent infections

doi:10.1016/S0022-3476(05)82151-1

The Journal of Pediatrics

Volume 118, Issue 3, March 1991, Pages 383-387

https://doi.org/10.1016/S0022-3476(05)82151-1 Get rights and content

Recombinant human interferon gamma enhances neutrophil respiratory burst and bactericidal activity in patients with chronic granulomatous disease. Mononuclear leukocytes of patients with the hyperimmunoglobulinemia E syndrome (Job syndrome) produce low or undetectable levels of this lymphokine. For these reasons we have restudied neutrophil chemotaxis in a group of our patients with the syndrome and determined the effect of recombinant human interferon gamma on the responses. Each of the patients had neutrophil chemotactic responses ranging from 22% to 55% of simultaneous control values (p<0.001). After incubation with interferon gamma, a significant improvement in chemotactic responsiveness was observed in the neutrophils of each of the patients (mean 301% of baseline chemotaxis; p<0.008). These data suggest the need for a double-blind, placebo-controlled trial of interferon gamma in a larger group of patients with the syndrome of hyperimmunoglobulinemia E and recurrent infections.

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Cited by (59)

STAT3 mutation-associated airway epithelial defects in Job syndrome
2023, Journal of Allergy and Clinical Immunology
Job syndrome is a disease of autosomal dominant hyper-IgE syndrome (AD-HIES). Patients harboring STAT3 mutation are particularly prone to airway remodeling and airway infections.
Airway epithelial cells play a central role as the first line of defense against pathogenic infection and express high levels of STAT3. This study thus interrogates how AD-HIES STAT3 mutations impact the physiological functions of airway epithelial cells.
This study created human airway basal cells expressing 4 common AD-HIES STAT3 mutants (R382W, V463del, V637M, and Y657S). In addition, primary airway epithelial cells were isolated from a patient with Job syndrome who was harboring a STAT3-S560del mutation and from mice harboring a STAT3-V463del mutation. Cell proliferation, differentiation, barrier function, bacterial elimination, and innate immune responses to pathogenic infection were quantitatively analyzed.
STAT3 mutations reduce STAT3 protein phosphorylation, nuclear translocation, transcription activity, and protein stability in airway basal cells. As a consequence, STAT3-mutated airway basal cells give rise to airway epithelial cells with abnormal cellular composition and loss of coordinated mucociliary clearance. Notably, AD-HIES STAT3 airway epithelial cells are defective in bacterial killing and fail to initiate vigorous proinflammatory responses and neutrophil transepithelial migration in response to an experimental model of Pseudomonas aeruginosa infection.
AD-HIES STAT3 mutations confer numerous abnormalities to airway epithelial cells in cell differentiation and host innate immunity, emphasizing their involvement in the pathogenesis of lung complications in Job syndrome. Therefore, therapies must address the epithelial defects as well as the previously noted immune cell defects to alleviate chronic infections in patients with Job syndrome.
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2018, Principles and Practice of Pediatric Infectious Diseases
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2014, Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
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2013, Emery and Rimoin's Principles and Practice of Medical Genetics
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2012, Principles and Practice of Pediatric Infectious Diseases, Fourth Edition
Host Defense Mechanisms Against Bacteria
2011, Fetal and Neonatal Physiology E-Book, Fourth Edition

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Supported by U.S. Public Health Service grants AI 13150 and AI19094, National Institute of Allergy and Infectious Diseases, and by Genentech, Inc.

Presented in part at the Annual Meeting of the Society for Pediatric Research, Washington, D.C., May 1989, and published in abstract form (Pediatr Res 1989; 25:164A).

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Original articleUse of recombinant human interferon gamma to enhance neutrophil chemotactic responses in Job syndrome of hyperimmunoglobulinemia E and recurrent infections*

Lancet

Lancet

Clin Immunol Immunopathol

J Allergy Clin Immunol

J Allergy Clin Immunol

Am J Med

Lancet

Severe staphylococcal disease associated with allergic manifestations, hyperimmunoglobulinemia E, and defective neutrophil chemotaxis

J Lab Clin Med

Infection, dermatitis, increased IgE, and impaired neutrophil chemotaxis

Arch Dermatol

Neutrophil chemotaxis in two patients with recurrent staphylococcal skin infections and hyperimmunglobulin E

J Lab Clin Med

Partial correction of the phagocytic defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma

N Engl J Med

Original article
Use of recombinant human interferon gamma to enhance neutrophil chemotactic responses in Job syndrome of hyperimmunoglobulinemia E and recurrent infections*