fSCIG 10% in pediatric primary immunodeficiency diseases: a European post-authorization safety study.

Background: The safety, tolerability, and immunogenicity of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% (dual-vial unit of human immunoglobulin 10% and recombinant human hyaluronidase [rHuPH20]) were assessed in children with primary immunodeficiency diseases (PIDs).

Methods: This phase 4, post-authorization, prospective, interventional, multicenter study (NCT03116347) conducted in the European Economic Area, enrolled patients aged 2 to < 18 years with a documented PID diagnosis who had received immunoglobulin therapy for ≥ 3 months before enrollment. New fSCIG 10% starters underwent fSCIG 10% dose ramp-up for ≤ 6 weeks (epoch 1) before receiving fSCIG 10% for ≤ 3 years (epoch 2); patients pretreated with fSCIG 10% entered epoch 2 directly.

Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.

Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.

Biallelic Cys141Tyr variant of SEL1L is associated with neurodevelopmental disorders, agammaglobulinemia, and premature death.

Suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) ER-associated degradation (ERAD) plays a critical role in many physiological processes in mice, including immunity, water homeostasis, and energy metabolism; however, its relevance and importance in humans remain unclear, as no disease variant has been identified. Here, we report a biallelic SEL1L variant (p. Cys141Tyr) in 5 patients from a consanguineous Slovakian family.

Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs), conferring a predisposition to life-threatening COVID-19 pneumonia. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52/IκBδ).

Severe congenital T-lymphocytopenia may affect the outcome of neonatal intensive care.

Aim: Circular DNA segments TREC (T-cell receptor excision circles) formed during T-lymphocyte maturation in the thymus, are a sensitive marker of thymic lymphocyte production in a broader manner. Quantification using qPCR is proposed as a surrogate marker of T cell malfunction in various primary and secondary conditions in a non-SCID selected risk newborn population.

Methods: We collected 207 dry blood spot samples during the years 2015-2018, from newly admitted risk newborns.

Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.

Background: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.

Objectives: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.

The importance of defining the age-specific TREC/KREC levels for detection of various inborn errors of immunity in pediatric and adult patients.

This study aimed to establish physiological TREC/KREC values in a healthy population of different ages to create cut-offs and analyze pediatric patients with various inborn errors of immunity. Dry blood spots and DNA samples purified from whole blood were used for TREC/KREC quantification using real-time PCR. Observed difference (p < 0.

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 Clinical and Genetic Spectrum of 82 Patients With Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries.

Variants in recombination-activating genes () are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency. We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the defects in populations inhabiting South, West, and East Slavic countries. Demographic, clinical, and laboratory data were collected from -deficient patients of Slavic origin via chart review, retrospectively.

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome.

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations.

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.

Dynamics of allergy development during the first 5 years of life.

Allergic diseases have increased in developed countries during the past decades. A cohort of Slovak children was followed from birth to track allergic symptoms dynamics in early childhood. Information on allergic symptoms (atopic dermatitis = AD, rhino conjunctivitis = RC, wheezing = Wh, urticaria = Ur) and food allergies among children was based on clinical evaluation of children by allergists at three developmental stages (infant, toddler, preschool).

Terminal 14q32.33 deletion as a novel cause of agammaglobulinemia.

Over the past decades, a pleiotropic spectrum of B-cell intrinsic defects leading to early onset agammaglobulinemia and absent B cells has been described. Herein we report terminal 14q32.33 deletion as a novel cause of agammaglobulinemia.

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].

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients.

Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options - a Retrospective Analysis.

Purpose: Nijmegen Breakage Syndrome (NBS) is a rare inherited condition, characterized by microcephaly, chromosomal instability, immunodeficiency, and predisposition to malignancy. This retrospective study, characterizing the clinical and immunological status of patients with NBS at time of diagnosis, was designed to assess whether any parameters were useful in disease prognosis, and could help determine patients qualified for hematopoietic stem cell transplantation.

Methods: The clinical and immunological characteristics of 149 NBS patients registered in the online database of the European Society for Immune Deficiencies were analyzed.

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.

Clinical picture and treatment of 2212 patients with common variable immunodeficiency.

Background: Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distribution and a high variability in clinical presentation. The main features include respiratory tract infections and their associated complications, enteropathy, autoimmunity, and lymphoproliferative disorders.

Objective: This study analyzes the clinical presentation, association between clinical features, and differences and effects of immunoglobulin treatment in Europe.

Periodic fever syndromes in Eastern and Central European countries: results of a pediatric multinational survey.

Objective: To analyze the prevalence of diagnosed and suspected autoinflammatory diseases in Eastern and Central European (ECE) countries, with a particular interest on the diagnostic facilities in these countries.

Methods: Two different strategies were used to collect data on patients with periodic fever syndromes from ECE countries- the Eurofever survey and collection of data with the structured questionnaire.

Results: Data from 35 centers in 14 ECE countries were collected.

Environmental and dietary risk factors for infantile atopic eczema among a Slovak birth cohort.

Infantile atopic eczema (AE) is a risk marker for future asthma. This study assesses the contribution of modifiable exposures to infantile AE. If modifiable exposures contribute substantially to infantile AE, its prevention might be a sensible approach to asthma prevention.