An Overlapping Syndrome of Allergy and Immune Deficiency in Children

Recurrent airway inflammations in children are an important clinical problem in pediatric practice. An essential challenge is differentiation between allergic background and immune deficiency, which is a difficult task taking into consideration individual predisposition to atopy, immune system maturation in the early childhood, as well as exposition to environmental allergens and microbial antigens. In this paper relationship between selected elements of innate and adaptive immunity, such as pattern-recognition receptors, complement components, dendritic cells, as well as immunoglobulins, and regulatory T lymph cells has been discussed. Particular attention has been paid to these mechanisms of the immune response which, depending on settings and timing of activation, predispose to allergy or contribute to tolerogenic phenotype. In the context of multifactorial conditioning of the innate and adaptive immunity governing the ultimate response and associations between allergy and immune deficiencies, these phenomena should be considered as pathogenetically not precluding, but as an overlapping syndrome

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

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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

A Novel CDC42 Mutation in an 11-Year Old Child Manifesting as Syndromic Immunodeficiency, Autoinflammation, Hemophagocytic Lymphohistiocytosis, and Malignancy: A Case Report

BACKGROUND: The CDC42 (Cell Division Cycle 42) gene product, CDC42, is a member of the family of small Rho GTPases, which are implicated in a broad spectrum of physiological functions in cell cycle regulation, including establishing and controlling of the cell actin cytoskeleton, vesicle trafficking, cell polarity, proliferation, motility and migration, transcription activation, reactive oxygen species production, and tumorigenesis. The CDC42 gene mutations are associated with distinct clinical phenotypes characterized by neurodevelopmental, growth, hematological, and immunological disturbances. CASE PRESENTATION: We report the case of an 11-year-old boy with syndromic features, immunodeficiency, and autoinflammation who developed hemophagocytic lymphohistiocytosis and malignant lymphoproliferation. In this patient, a novel heterozygous p.Cys81Tyr mutation in the CDC42 gene was found by whole exome sequencing. CONCLUSIONS: The Cdc42 molecule plays a pivotal role in cell cycle regulation and a wide array of tissue-specific functions, and its deregulation may result in a broad spectrum of molecular and cellular dysfunctions, making patients with CDC42 gene mutations susceptible to infections, immune dysregulation, and malignancy. In the patient studied, a syndromic phenotype with facial dysmorphism, neurodevelopmental delay, immunodeficiency, autoinflammation, and hemophagocytic lymphohistiocytosis shares common features with Takenouchi–Kosaki syndrome and with C-terminal variants in CDC42. It is important to emphasize that Hodgkin's lymphoma is described for the first time in the medical literature in a pediatric patient with the novel p.Cys81Tyr mutation in the CDC42 gene. Further studies are required to delineate precisely the CDC42 genotype–phenotype correlations