Aleksandra Szczawińska-Popłonyk

The hyperimmunoglobulin E syndrome - clinical manifestation diversity in primary immune deficiency

The hyper-IgE syndromes are rare, complex primary immunodeficiencies characterized by clinical manifestation diversity, by particular susceptibility to staphylococcal and mycotic infections as well as by a heterogeneous genetic origin. Two distinct entities - the classical hyper-IgE syndrome which is inherited in an autosomal dominant pattern and the autosomal recessive hyper-IgE syndrome have been recognized. The autosomal dominant hyper-IgE syndrome is associated with a cluster of facial, dental, skeletal, and connective tissue abnormalities which are not observable in the recessive type. In the majority of affected patients with autosomal dominant hyper-IgE syndrome a mutation in the signal transducer and the activator of the transcription 3 gene has been identified, leading to an impaired Th17 cells differentiation and to a downregulation of an antimicrobial response. A mutation in the dedicator of the cytokinesis 8 gene has been identified as the cause of many cases with autosomal recessive hyper-IgE syndrome and, in one patient, a mutation in tyrosine kinase 2 gene has been demonstrated. In this paper, the authors provide a review of the clinical manifestations in the hyper-IgE syndromes with particular emphasis on the diversity of their phenotypic expression and present current diagnostic guidelines for these diseases.

Neurotrophin serum concentrations and polymorphisms of neurotrophins and their receptors in children with asthma

BACKGROUND In the recent years numerous studies have analysed the effects of neurotrophins on allergic inflammation in airway diseases reporting increased neurotrophin levels locally in the airways as well as in serum of asthmatic patients. We aimed to investigate if levels of neurotrophins in serum of asthmatic children are influenced by the genotype of functional variants within genes encoding analysed neurotrophins and their specific receptors. METHODS In the study we included 98 children diagnosed with asthma. Genotyping of 9 polymorphisms located in neurotrophins genes and their receptors genes was done with use of TaqMan SNP genotyping assays or PCR-RFLP. The serum levels of four neurotrophins (BDNF, NGF, NTF3, NTF4) were analysed during exacerbation of asthma symptoms with use of DuoSet ELISA Development Kit (R&D). RESULTS The two patients with the genetic variant A/A of NTRK1 (rs6334) showed significantly higher NGF serum concentrations (113.4 and 218.1 pg/mL) as compared to the mean NGF serum concentrations in the total group of patients (34.8 pg/mL). We also observed a significant epistatic interactions between variants of NGF rs6330 and NTRK1 rs6334 that influenced NGF serum level (P = 0.0004). Analysis of four neurotrophins serum levels in relation to different genotypes of analysed neurotrophins genes showed no significant differences among analysed asthmatic children. CONCLUSIONS Our results suggest that, among analysed neurotrophins, NGF serum levels may be influenced by the genotype of NTRK1 gene individually as well as in the interaction with NGF functional genetic variant suggesting their involvement in allergic inflammation in asthma. Serum levels of the other neurotrophins do not seem to be affected by the variants in the analysed genes.

Prevalence of Helicobacter pylori infection in patients with cystic fibrosis

INTRODUCTION Helicobacter pylori (H. pylori) is one of the most common bacterial infections worldwide. The prevalence of Hp infection in cystic fibrosis (CF) is unclear. Thus, the aim of our study was to determine the prevalence of H. pylori infection in CF patients and to correlate H. pylori presence with CF expression. MATERIAL AND METHODS The presence of H. pylori infection was assessed using a breath test with isotope-labeled urea in CF 79 patients compared to 302 healthy control subjects (HS). RESULTS Fifteen (19.0%) CF patients were H. pylori positive. No statistical differences in the basic clinical parameters or in their distribution were documented. No clinical factor was an independent risk factor of H. pylori infection. The corrected prevalence of H. pylori infection in pediatric CF patients and HS was 14.4% and 9.8%, respectively. CONCLUSION The prevalence of H. pylori infection in CF patients is not different from that in healthy subjects.

Hyper Ig E syndrome (Job syndrome, HIES) - radiological images of pulmonary complications on the basis of three cases

Summary Background: Hyperimmunoglobulinemia E syndrome (hyper-IgE syndrome, Job syndrome, HIES) is a complex immune deficiency with multiorgan clinical manifestations and diverse genetic background. The clinical triad of symptoms observed in approximately 75% of patients with HIES includes: recurrent abscesses of staphylococcal etiology, recurrent respiratory infections and elevated immunoglobulin E in serum. Case Report: The paper discusses three cases of female patients presenting typical pulmonary complications of the hyper-Ig E syndrome. In the first case, the development of aspergilloma in a postinflamatory cyst was observed, in the other one, pneumonia with pleural effusion, and as a consequence of inflammatory infiltrations – fibrotic changes, giving rise to lobectomy, while in the last of these cases, the course of lung disease was complicated by formation of staphylococcal abscess. In one of the girls, bronchiectasis appeared at follow-up. Conclusions: Complications of pulmonary infections are the most common causes of death in hyper-Ig E syndrome. Late diagnosis significantly worsens the respiratory function and reduces the chance for normal development of a child. Introduction of comprehensive treatment, including prophylaxis, decreases the recurrences. Therefore, the important role is attributed to the radiologist in the multidisciplinary care of patients with this syndrome.

Pulmonary Lymphomatoid Granulomatosis in Griscelli Syndrome Type 2

Griscelli syndrome type 2 (GS2) is a rare autosomal-recessive disorder associated with a RAB27A gene mutation, and clinically manifesting as hypopigmentation, disseminated chronic encephalitis, and severe immunological disorders characterized by an accelerated hematological phase, also referred to as hemophagocytic syndrome (HS), or hemophagocytic lymphohistiocytosis (HLH). The authors report the diagnosis of GS2 in an 11-year-old girl with hypopigmentation, immunodeficiency, hepatosplenomegaly, severe neurological impairments, and fatal multiorgan failure. In this patient a diagnosis of pulmonary lymphomatoid granulomatosis (LG), an Epstein-Barr virus (EBV)-related lymphoproliferative disorder, was established from radiological and histological findings. Although EBV-related malignancies are common in immunocompromised patients, this is the first report of a diagnosis of pulmonary LG in a patient with GS2.

Oral manifestations of primary immune deficiencies in children

An important task for both dentists and pediatricians dealing with patients manifesting different oral lesions is to be able to differentiate changes signaling systemic disease from those appearing without any concomitant serious health problem. In this article, symptomatology of selected primary immune deficiency diseases are discussed with particular emphasis on oral manifestations reported in this group of disorders. Facial, dental, and oral findings compose a constellation of symptoms observed in immunodeficiency diseases. Predisposition to bacterial invasion, cytokine dysregulation, tissue inflammatory process, and necrosis lead to early-onset oral lesions and periodontitis. Developmental abnormalities, periodontal disease, and oral lesions may accompany immunodeficiency and require particular awareness directed toward diagnosis of an underlying disease of the immune system.

Impaired antigen-specific immune response to vaccines in children with antibody production defects

ABSTRACT The impaired synthesis of antigen-specific antibodies, which is indispensable for an adaptive immune response to infections, is a fundamental pathomechanism that leads to clinical manifestations in children with antibody production defects. The aim of this study was to evaluate the synthesis of antigen-specific antibodies following immunization in relation to peripheral blood B cell subsets in young children with hypogammaglobulinemia. Twenty-two children, aged from 8 to 61 months, with a deficiency in one or more major immunoglobulin classes participated in the study. Postvaccination antibodies against tetanus and diphtheria toxoids, the surface antigen of the hepatitis B virus, and the capsular Haemophilus influenzae type b polysaccharide antigen were assessed along with an immunophenotypic evaluation of peripheral blood B lymph cell maturation. A deficiency of antibodies against the tetanus toxoid was assessed in 73% of cases and that against the diphtheria toxoid was assessed in 68% of cases, whereas a deficiency of antibodies against the surface antigen of the hepatitis B virus was revealed in 59% of the children included in the study. A defective response to immunization with a conjugate vaccine with the Haemophilus influenzae type b polysaccharide antigen was demonstrated in 55% of hypogammaglobulinemic patients. Increased proportions of transitional B lymph cells and an accumulation of plasmablasts accompanied antibody deficiencies. The defective response to vaccine protein and polysaccharide antigens is a predominating disorder of humoral immunity in children with hypogammaglobulinemia and may result from a dysfunctional state of the cellular elements of the immune system.

Cytomegalovirus pneumonia as the first manifestation of severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) is characterized by the absence of functional T lymphocytes and impairment of adaptive immunity. While heterogeneity of the genetic background in SCID leads to the variability of immune phenotypes, most of affected newborns appear healthy but within the first few months they develop life-threatening opportunistic respiratory or gastrointestinal tract infections. The objective of the study was to define the presenting features and etiology of infections in children with SCID. We retrospectively reviewed five children in whom the diagnosis of SCID had been established in our pediatric immunology clinic over the last 10-year period. A viral respiratory tract infection was the first manifestation of SCID in all the children studied. Cytomegalovirus (CMV) pneumonia was recognized in as many as 4 cases and coronavirus pulmonary infection was diagnosed in one case, whereas Pneumocystis jiroveci was identified as a co-pathogen in one CMV-infected patient. Severe combined immunodeficiency is a pediatric emergency condition and given the significant impact of pulmonary CMV infection in SCID children, establishing an accurate etiological diagnosis is of essential importance in instituting the specific treatment and improving the outcome.

Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency.

Please cite this paper as: Szczawinska‐Poplonyk et al. (2012) Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12059.

Pulmonary manifestation of immunoglobulin G4-related disease in a 7-year-old immunodeficient boy with Epstein-Barr virus infection: a case report.

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is a multiorgan fibroinflammatory condition with lymphoplasmacytic infiltrates containing abundant IgG4-positive plasma cells. The immunopathogenesis of the disease and the potential role of triggering autoantigens or infectious factors have not been clearly defined. Immunoglobulin G4-related lung disease is a new and emerging condition in pediatric patients and to date, there have been only two reports regarding pulmonary manifestation of IgG4-RD in children recently published. This is the first report of IgG4-related lung disease in an immunodeficient child with Epstein-Barr virus infection.Case presentationWe report on the case of a 7-year old atopic boy who was hospitalized with an initial clinical and radiological diagnosis of pneumonia, positive Epstein-Barr virus (EBV)-DNA in the blood and defective adaptive immunity. The lung CT showed a consolidated mass lesion adjacent to the posterior wall of the chest and the diaphragm. The child underwent surgical resection of the tumor, and the histologic examination of the lung specimens revealed lymphoplasmacytic infiltrates with fibrosis and vasculitis correlating with IgG4-related lung disease. Subsequent monitoring of the patient with lung CT, pulmonary function tests and IgG4 levels did not show signs of active disease.ConclusionsThe diagnosis of IgG4-related lung disease in children is challenging because of its rarity, nonspecific symptomatology and heterogeneous morphological manifestations. Further studies are required in children with pulmonary presentation of IgG4-RD to better understand pathogenesis of this condition, possible immunological or infectious triggering factors, and finally, to determine pediatric patient-targeted therapeutic interventions.