title: No indication for a defect in toll-like receptor signaling in patients with hyper-IgE syndrome.
abstract: Hyper-IgE syndrome is a rare primary immunodeficiency of unknown etiology characterized by recurrent infections of the skin and respiratory system, chronic eczema, elevated total serum IgE, and a variety of associated skeletal symptoms. Recent reports about susceptibility to pyogenic bacterial infections and high IgE levels in patients and animals with defects in toll-like receptor (TLR) signaling pathways prompted us to search for TLR signaling defects as an underlying cause of hyper-IgE syndrome. Blood samples from six patients with hyper-IgE syndrome were analyzed for serum cytokine levels, intracellular cytokine production in T cells after stimulation with PMA/ionomycin, and cytokine production from peripheral blood mononuclear cells stimulated by TLR ligands and bacterial products including LPS (TLR4), peptidoglycan (TLR2), PolyIC (TLR3), R848 (TLR7/8), CpG-A, and CpG-B (TLR9), zymosan and heat killed Listeria monocytogenes. All results were compared to data from healthy controls. A reduction in IFN-gamma, IL-2, and TNF-alpha producing T cells after PMA stimulation suggested a reduced inflammatory T cell response in patients with hyper-IgE syndrome. Increased serum levels of IL-5 indicated a concomitant Th2 shift. However, normal production of cytokines (TNF-alpha, IL-6, IL-10, IFN-alpha, IP-10) and upregulation of CD86 on B cells and monocytes after TLR stimulation made a defect in TLR signaling pathways highly unlikely. In summary, our data confirmed an imbalance in T cell responses of patients with hyper-IgE syndrome as previously described but showed no indication for an underlying defect in toll-like receptor signaling.
authors.affiliation: University Children's Hospital, Dr. von Haunersches Kinderspital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: E D
authors.initials: ED
authors.lastname: Renner
authors.forename: I
authors.initials: I
authors.lastname: Pawlita
authors.forename: F
authors.initials: F
authors.lastname: Hoffmann
authors.forename: V
authors.initials: V
authors.lastname: Hornung
authors.forename: D
authors.initials: D
authors.lastname: Hartl
authors.forename: M
authors.initials: M
authors.lastname: Albert
authors.forename: A
authors.initials: A
authors.lastname: Jansson
authors.forename: S
authors.initials: S
authors.lastname: Endres
authors.forename: G
authors.initials: G
authors.lastname: Hartmann
authors.forename: B H
authors.initials: BH
authors.lastname: Belohradsky
authors.forename: S
authors.initials: S
authors.lastname: Rothenfusser
mesh_terms: D000293:Adolescent; D000328:Adult; D002177:Candidiasis / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007223:Infant; D007589:Job Syndrome / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D008024:Ligands; D008297:Male; D015398:Signal Transduction / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism / Q000502:physiology*
chemical_list: D016207:Cytokines; D008024:Ligands; D051193:Toll-Like Receptors; D007073:Immunoglobulin E