Immunologic phenotype of a child with the MEHMO syndrome.

MEHMO syndrome is a rare X-linked syndrome characterized by Mental retardation, Epilepsy, Hypogenitalism, Microcephaly, and Obesity associated with the defect of protein synthesis caused by the EIF2S3 gene mutations. We hypothesized that the defect in protein synthesis could have an impact on the immune system. We describe immunologic phenotype and possible treatment outcomes in patient with MEHMO syndrome carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. The proband (currently 9-year-old boy) had normal IgG and IgM levels, but had frequent respiratory and urinary tract infections. On subcutaneous immunoglobulin therapy achieving supra-physiological IgG levels the frequency of infections significantly decreased in Poisson regression by 54.5 % (CI 33.2-89.7, p=0.017). The MEHMO patient had had frequent acute infections despite normal IgG and IgM serum levels and responded well to the immunoglobulin treatment.

Correction to: Primary immunodeficiencies in Central and Eastern Europe-the power of networking Report on the activity of the Jeffrey Modell Foundation Centers Network in Central and Eastern Europe.

Due to authors' internal mistake they have misspelled the name of one of the co-authors in this article.

Primary immunodeficiencies in Central and Eastern Europe-the power of networking Report on the activity of the Jeffrey Modell Foundation Centers Network in Central and Eastern Europe.

Jeffrey Modell Foundation centers' network activities in Central and Eastern Europe (JMF CEE) have contributed to the development of care for patients with primary immunodeficiencies. On the data continuously collected from individual centers in participating countries since 2011, we demonstrate a steady improvement in a number of aspects concerning complex care for patients with primary immunodeficiencies. The presented data show an improvement of awareness about these rare diseases across the whole Central and Eastern European region, an increase in newly diagnosed patients as well as genetically confirmed cases, earlier establishment of diagnosis, and improved access to clinical treatment. We also present an active patient involvement that is reflected in the expansion of patient organization centers and their activities. The cooperation within the JMF CEE network has also contributed to greater international exposure of participating centers and further to the gradual development of research activities in the rapidly evolving field of primary immunodeficiencies. The improvement of all important aspects of the complex field of primary immunodeficiencies within the JMF CEE network documents the strength and advantages of the joint and coordinated networking.

Impact of interleukin 13 (IL13) genetic polymorphism Arg130Gln on total serum immunoglobulin (IgE) levels and interferon (IFN)-γ gene expression.

This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in interleukin (IL)-4/IL-13 signalling pathways leading to atopic disease in early childhood. We evaluated involvement of five single nucleotide polymorphisms IL4 C-590T, IL13 C-1055T, IL13 Arg130Gln, IL4RA Ile50Val and IL4RA Gln576Arg, in the control of serum total and antigen-specific immunoglobulin (Ig)E levels. Furthermore, we analysed their association with changes in gene expression of five cytokines having key roles in inflammatory and anti-inflammatory immune response [IL-4, IL-13, interferon (IFN)-γ, IL-8 and IL-10]. Total and antigen-specific IgE levels in serum and gene expression of selected cytokines in peripheral blood were measured in 386 children aged 1-8 years. TaqMan allelic discrimination, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphisms (RFLP) methods validated by sequencing were used for genotyping. All genotypes for children with total and antigen-specific IgE levels in the normal range were in Hardy-Weinberg equilibrium. Gene expression analyses were carried out using TaqMan gene expression assays. We found elevated total IgE levels in carriers of IL13 Arg130Gln variant allele [odds ratio (OR) = 1·84; 95% confidence interval (CI) = 1·16-2·93]. This effect was more apparent for boys (OR = 2·31; 95% CI = 1·25-4·28). However, no significant association was observed for the other four variants examined. We found up-regulation of IFN-γ in children with elevated serum total IgE levels carrying the Arg130 allele (P = 0·005). No differences were found for IL4, IL8 or IL10, while IL13 gene expression was under the detection limit. IL13 Arg130Gln genotypes can play a role in genetic susceptibility to allergy via regulation of serum total IgE levels and affecting IFN-γ gene expression.

Systemic Listeria monocytogenes infection in a 2-year-old immunocompetent child.

Central nervous system infection and sepsis are the most frequently observed clinical presentations of listeriosis infection; however, they are rare in immunocompetent children beyond the neonatal period. In the presented case, we described gastrointestinal involvement, subacute meningitis, sinusitis and sepsis in a two-year-old previously healthy child with acute infection caused by Listeria monocytogenes. We suggest that the infection was probably enhanced by an inappropriate corticosteroid treatment at the onset of the disease, while immunological testing did not confirm the primary deficiency of cellular immunity.

Saethre-Chotzen syndrome and hyper IgE syndrome in a patient with a novel 11 bp deletion of the TWIST gene.

Molecular genetic studies in a seven-year-old boy and his mother demonstrated a novel 11 bp deletion in the TWIST gene (127del11), causing Saethre-Chotzen syndrome. The mother had rather mild signs of the Saethre-Chotzen syndrome; however, her son presented with marked acrocephalosyndactyly type 3, leading to craniotomy at three years. He also had recurrent infections and laboratory findings comparable with the hyper IgE syndrome, a rare primary immunodeficiency disorder. It is likely that the 11bp deletion caused the Saethre-Chotzen syndrome in the patient and his mother, and another, not yet identified genetic defect, seen in the patient but not in the mother, is responsible for the hyper IgE phenotype. A combination of these two congenital conditions has not been described to date.

Cord serum immunoglobulin E related to the environmental contamination of human placentas with organochlorine compounds.

Allergic diseases are on the rise in both prevalence and severity, especially in industrialized countries. The process of allergic sensitization needs an understanding of the role environmental factors play in its development. In addition to traditionally considered air pollutants, various persistent organochlorine pollutants, which accumulate in the human body over a lifetime via food intake, are toxic in humans. Placental contamination by chemicals may act as a biologic marker for the exposure of the mother or for the fetus via transplacental transfer. Placentas were collected from term deliveries in two Slovak regions. The samples were then analyzed for 21 selected organochlorine compounds. Specimens of cord blood from 2,050 neonates were gathered for the determination of levels of total immunoglobulin E (IgE). The regions were chosen according to their environmental characteristics: a city polluted with organic chemical industry versus a rural region devoid of industrial sources of pollution. In addition, data regarding the incidence rate of atopic eczema cases in the regions were considered. Comparisons between regions revealed that both the placental contamination with 16 of 21 organochlorine compounds and the cord serum IgE levels were significantly higher in the industrial region. The findings pointed to an association between organochlorine compounds and the higher levels of total IgE in newborns, signaling a higher allergic sensitization in the industrial region. This association was supported by the higher incidence rate of atopic eczema cases in the population registered in the industrial region.