Selective insufficiency of IFN-gamma secretion in patients with hyper-IgE syndrome.
BACKGROUND
Hyper-immunoglobulin E (IgE) syndrome is a complex immune deficiency characterized by chronic eczematous dermatitis, recurrent staphylococcal infections, pneumatoceles, reduced neutrophil chemotaxis, and variably impaired T cell function. Although decreased interferon-gamma (IFN-gamma) production in patients with hyper-IgE syndrome is pointed out and known as a cause of reduced neutrophil chemotaxis, precise mechanism of their inadequate production of IFN-gamma remains unknown. To elucidate the pathogenesis of the defective production of IFN-gamma in patients with hyper-IgE syndrome, we assessed the in vitro production and secretion of IFN-gamma by peripheral blood mononuclear cells (PBMCs) from patients with hyper-IgE syndrome.


METHODS
Chemotaxis of neutrophils, mRNA levels of several cytokines, intracellular production and extracellular secretion of IFN-gamma, interleukin-2 (IL-2), and IL-4 by PBMCs from three patients with hyper-IgE syndrome were determined.


RESULTS
The transcription of IFN-gamma mRNA and the production of its protein molecules progressed normally. However, selective insufficiency in the secretion of IFN-gamma molecules was found in patients with hyper-IgE syndrome. Confocal laser scanning microscopy clearly demonstrated the accumulation of IFN-gamma in patients with hyper-IgE syndrome.


CONCLUSIONS
We demonstrated that there was a selective insufficiency in the secretion of IFN-gamma in patients with hyper-IgE syndrome. We hope that this fact would offer a new paradigm for understanding this disease.
Ito
R
R
Department of pediatrics, Yokohama City University School of Medicine, Fukuura kanazawaku Yokohama city, Japan.
Mori
M
M
Katakura
S
S
Kobayashi
N
N
Naruto
T
T
Osamura
Y
Y
Aihara
Y
Y
Yokota
S
S
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D002633:Chemotaxis; D002648:Child; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009504:Neutrophils / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins; D013577:Syndrome
D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma