STAT3 couples with 14-3-3σ to regulate BCR signaling,B-cell differentiation,and IgE production

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Analysis of T-lymphocyte subtypes of the peripheral blood and skindelayed-type hypersensitivity in patients with hyper-IgE syndrome

INTRODUCTIONH yperimmunoglobulin E ( Hyper IgE, HIE ) syn drome is a rare, primary immunodeficiency dis ease. Thus far, about 200 cases have been reportedworldwide. It is a multi system disorder characterized byeczema, recurrent staphylococcal infections, pneumato celes, and reduced neutrophil chemotaxis. The most sig nificant feature of this syndrome is that the elevatedserum levels of IgE are uniformly found[1]. Although itis an immunodeficiency disease, …     

Aberrant humoral immune reactivity in DOCK8 deficiency with follicular hyperplasia and nodal plasmacytosis

Mutations in the DOCK8 gene define the most common form of autosomal-recessive Hyper-IgE-syndrome (AR-HIES/OMIM#243700). In a patient with extensive molluscum contagiosum lesions, a homozygous DOCK8 gene deletion was demonstrated.     

Staphylococcal scalded skin syndrome: An uncommon symptomatology revealing an immune deficiency

Primary immune deficiencies associated with hyper-IgE syndrome are rare diseases with clinical features dominated by recurring cutaneous and visceral bacterial infections, particularly infections due to Staphylococcus species. Most of these infections are associated with milder inflammation compared to normal. We report a primary immune deficiency associated with a hyper-IgE syndrome revealed by a staphylococcal scalded skin syndrome in a 5-year-old girl. The patient presented with a severe staphylococcal infection with extensive skin lesions and disseminated intravascular coagulation. She received intravenous fluids to compensate for fluid losses and anti-staphylococcal antibiotics. Coagulopathy was also corrected. However, the progression was rapidly fatal.     

Treatment of hyper-IgE dermatitis with interferon-γ

Background Interferon-γ has been suggested as causal therapy in both hyper-IgE syndrome and severe atopic dermatitis. Aim To investigate the therapeutic effect of short-term, low-dose interferon-γ both as monotherapy and in combination with topical treatment, in a patient with a variant of the hyper-IgE syndrome. Method Interferon-γ was administered subcutaneously (50 μ/m² X 3 d/w) for 4 weeks. Three regions were studied: hands, flank and feet. The hands were treated with betamethasone-17–valerate cream and the feet with mupirocin ointment, while the flank was treated only with a moisturizer. Results All regions showed significant reductions of the clinical scores (0.0001 < P < 0.0280), but hands and feet showed significantly greater reduction than Hank (P < 0.004). Conclusions The results suggest that short-term, low-dose interferon-γ treatment is a potentially useful therapy in hyper-IgE syndrome dermatitis when used in combination with topical mupirocin or a steroid.     

Hyper-IgE syndrome and autoimmunity in Mexican children

Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by recurrent skin abscesses, recurrent pneumonia with pneumatocele formation, eczema, eosinophilia, and elevated levels of serum IgE. Patients with the autosomal recessive (AR) form of HIES appear to be prone to developing autoimmune diseases. We present two cases of HIES with autoimmune complications; one case was a product of a consanguineous marriage, the other one was a sporadic case. The first patient presented with recurrent episodes of erythema nodosum, warts, bronchiolitis obliterans and thrombocytopenia. The second patient developed glomerulonephritis resulting in endstage renal failure. She later developed malar rash, oral ulcers, cerebral infarcts with vasculitis and positive ANA, anti-dsDNA, and antiphospholipid antibodies. We discuss the dilemma in treating patients who present with both primary immunodeficiency and autoimmunity.     

No Indication for a Defect in Toll-Like Receptor Signaling in Patients with Hyper-IgE Syndrome

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-γ, IL-2, and TNF-α 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-α, IL-6, IL-10, IFN-α, 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.     

4例高IgE综合征的临床分析和基因诊断

目的 探讨高IgE综合征(hyper-IgE syndrome,HIES)的临床特征和基因诊断价值.方法 用NIH评分系统对2009年1-7月在重庆医科大学附属儿童医院就诊的4例(男性3例,女性1例)疑似HIES患儿进行评分,总分大于40分为临床诊断标准.用RT-PCR及PCR直接测序法,分析患儿STAT3基因.结果 ...