Molecular Assessment of Staphylococcus Aureus Strains in STAT3 Hyper-IgE Syndrome Patients.

Hyper-IgE syndromes (HIES) are a group of inborn errors of immunity (IEI) caused by monogenic defects such as in the gene STAT3 (STAT3-HIES). Patients suffering from HIES show an increased susceptibility to Staphylococcus aureus (S. aureus) including skin abscesses and pulmonary infections.

A structured patient empowerment programme for primary immunodeficiency significantly improves general and health-related quality of life.

Introduction: Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases characterized by increased susceptibility to infections and a reduced quality of life (QoL). The influence of a patient empowerment programme for PID (PID-PEP) on general and health-related QoL was assessed in the present study.

Material And Methods: PID-PEP is provided by a multidisciplinary team for patients with PID and immunoglobulin G (IgG) replacement therapy during a weekend course to improve patient self-management regarding chronic disease and long-term therapy.

High seroprevalence of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) among HIV-1-infected children and adolescents in a non-endemic population.

Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS), which primarily affects human immunodeficiency virus (HIV)-infected adults with advanced immunodeficiency. Currently, only limited prevalence data for HHV-8 infection in HIV-infected children living in non-endemic areas are available. This multicenter cross-sectional study was conducted in four university hospitals in Germany specializing in pediatric HIV care.

Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections.

DOCK8 deficiency: clinical and immunological phenotype and treatment options - a review of 136 patients.

Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.

Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry.

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994.

HIV-1 seroreversion in HIV-1-infected children: do genetic determinants play a role?

Background: HIV-1 seroreversion in infants with vertically transmitted HIV-1 infection who started ART in the first months of life has been reported in only a subset of patients. However, the reason why most infants remain seropositive despite similar treatment response is not understood. Here, we assessed whether HIV-1 seroreversion in maternally infected infants is associated with genetic determinants.

A novel gain-of-function IKBA mutation underlies ectodermal dysplasia with immunodeficiency and polyendocrinopathy.

Purpose: This study reports the identification of a novel heterozygous IKBA missense mutation (p.M37K) in a boy presenting with ectodermal dysplasia with immunodeficiency (EDA-ID) who had wild type IKBKG gene encoding NEMO. Our aim was to characterize the clinical course of this IκB-α gain-of-function mutant and to investigate if the p.

The German national registry for primary immunodeficiencies (PID).

In 2009, a federally funded clinical and research consortium (PID-NET, http://www.pid-net.org) established the first national registry for primary immunodeficiencies (PID) in Germany.

[Guideline for antiretroviral therapy of HIV-infected children and adolescents].

The HIV-infection in adults or children and adolescent differs substantially. Differences include the mode of infection, viral dynamics facing a developing immune system and the clinical course of the infection. In addition to the virological, immunological and epidemiological aspects the psychosocial situation is also very different.

Phylodynamic and phylogeographic patterns of the HIV type 1 subtype F1 parenteral epidemic in Romania.

In the late 1980s an HIV-1 epidemic emerged in Romania that was dominated by subtype F1. The main route of infection is believed to be parenteral transmission in children. We sequenced partial pol coding regions of 70 subtype F1 samples from children and adolescents from the PENTA-EPPICC network of which 67 were from Romania.

Successful long-term correction of autosomal recessive hyper-IgE syndrome due to DOCK8 deficiency by hematopoietic stem cell transplantation.

Autosomal dominant hyper-IgE syndrome (AD-HIES), characterised by eczema, increased susceptibility to skin and lung infections, elevated IgE and skeletal abnormalities is associated with heterozygous STAT3 mutations. The autosomal recessive variant (AR-HIES) has similar immunological findings but mainly lacks extraimmune manifestations. Several AR-HIES patients have recently been shown to harbour mutations in the gene for dedicator of cytokinesis 8 (DOCK8).

X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease.

X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome.

ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasia.

Background: Defects in the development or activation of T cells result in immunodeficiency associated with severe infections early in life. T-cell activation requires Ca2+ influx through Ca2+-release activated Ca2+ (CRAC) channels encoded by the gene ORAI1.

Objective: Investigation of the genetic causes and the clinical phenotype of immunodeficiency in patients with impaired Ca2+ influx and CRAC channel function.

Successful SCT for Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is characterized by chromosomal instability, radiation hypersensitivity, characteristic facial appearance, immunodeficiency and strong predisposition to lymphoid malignancy. Traditionally, NBS patients have not undergone hematopoietic SCT (HSCT) owing to concerns about increased toxicity. We therefore report on the HSCT experience in NBS patients in Europe.

Common variable immunodeficiency disorders in children: delayed diagnosis despite typical clinical presentation.

Objective: To characterize common variable immunodeficiency disorder (CVID) in childhood.

Study Design: We retrospectively investigated clinical findings in 32 children with primary CVID by questionnaire and file review.

Results: Clinical presentation included recurrent or chronic respiratory tract infections (88%), sinusitis (78%), otitis media (78%), and intestinal tract infections (34%), mainly with encapsulated bacteria.

Disease progression in HIV-1 infected children and adolescents--results of a German-Austrian cohort study.

Objective: The Paediatric Working Group AIDS (PAAD) initiated a prospective cohort study in order to investigate disease progression in HIV- infected children and adolescents and the effect of antiretroviral treatment regimes.

Patients And Methods: Between 1998 and 2003, paediatric centres documented HIV-infected patients under clinical care using a questionnaire for basic data and annual follow up. Main outcome measures were: use of antiretroviral therapy, adverse events, disease progression and change of therapeutic regimes.

Long-term posaconazole treatment and follow-up of rhino-orbital-cerebral mucormycosis in a diabetic girl.

To demonstrate that the 2-yr clinical follow-up of our patient strongly suggests that long-term therapy with posaconazole (POS) is safe and beneficial in treatment and prevention of relapses of, otherwise fatal, central nervous system mucormycosis. Mucormycosis is a very rare opportunistic mycotic infection of diabetic children. We present the 30-month follow-up of a 12-yr-old girl affected by diabetic ketoacidotic coma, complicated by rhinocerebral mucormycosis and successfully treated with POS at the initial daily dose of 5 mg/kg t.

Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIV-infected children.

Objectives: To obtain data on the pharmacokinetics of efavirenz in children in clinical practice.

Methods: HIV-1-infected children received efavirenz capsules or tablets in accordance with manufacturer's dosing recommendations. Plasma was collected at regular visits and analysed by HPLC.

Increased rate of prematurity associated with antenatal antiretroviral therapy in a German/Austrian cohort of HIV-1-infected women.

Objective: The aim of the study was to assess the risk of adverse pregnancy outcomes after antenatal antiretroviral therapy in a well-defined prospective cohort of nontransmitting HIV-infected women.

Methods: Prospective monitoring of 183 mother-child pairs from 13 centres in Germany and Austria, delivering between 1995 and 2001, was carried out. Following German-Austrian guidelines recommending an elective Caesarean section (CS) at 36 weeks, prematurity was defined as <36 weeks' gestation for these analyses.