Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Neuroblastoma Occurring in Nijmegen Breakage Syndrome.

Nijmegen breakage syndrome (NBS) is a rare primary immunodeficiency disease due to a pathogenic variant in the NBN gene causing impaired DNA repair and increased predisposition for lymphoid malignancy. By contrast, solid tumors have been rarely reported. Neuroblastoma (NB) is a rare childhood solid tumor, associated with the worse outcome if MYCN oncogene is amplified.

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.

Mechanisms of redox balance and inflammatory response after the use of methylprednisolone in children with multisystem inflammatory syndrome associated with COVID-19.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with being infected with coronavirus-19 (COVID-19) is a life-threatening condition resulting from cytokine storm, increased synthesis of reactive oxygen species (ROSs), and hyperinflammation occurring in genetically predisposed children following an infection with SARS-CoV-2.

Aim: The primary aims of our study were to identify changes in the activity of antioxidant enzymes in erythrocytes and total oxidative status in plasma after being treated with methylprednisolone (MP).

Methods: A prospective cohort study of 67 children (56.

Association of Antiphospholipid Antibodies with Clinical Manifestations in Children with Systemic Lupus Erythematosus.

Background: The aim of the study is to evaluate the effect of the presence of antiphospholipid antibodies on the clinical and laboratory manifestations, disease activity and outcomes of the disease in patients with childhood-onset systemic lupus erythematosus (cSLE).

Methods: We conducted a 10-year cross-sectional study with a retrospective analysis of clinical and laboratory parameters and outcome of the disease (kidney, nervous system involvement, thrombosis). For the purpose of the study, patients were divided into cohort groups based on the presence of antiphospholipid antibodies (aPLA), named the aPLA positive group, or their absence, named the aPLA negative group.

Analysis of cardiac manifestation and treatment of multisystem inflammatory syndrome in children related to SARS-CoV-2.

Cardiovascular manifestations are common (35-100%) in the multisystem inflammatory syndrome in children. Our study aimed to analyze treatment impact and cardiovascular involvement in patients with multisystem inflammatory syndrome in children. The retrospective cohort included 81 patients treated between April 2020 and December 2021 (9.

Case Report: Early Onset Systemic Lupus Erythematosus Due to Hereditary C1q Deficiency Treated With Fresh Frozen Plasma.

Hereditary C1q deficiency is associated with early-onset autoimmunity causing SLE or SLE-like disease as well as increased risk for infections with encapsulated bacteria. It is a rare genetic condition inherited in an autosomal recessive manner, caused by mutations in C1q genes. Treatment and management of this rare disease are very complex and include prophylactic vaccination, antibiotics, and immunosuppressive drugs.

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.

Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib.

Background: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation.

Secondary hemophagocytic lymphohistiocytosis in a child with Leptospira infection: A case report.

Jevtic D, Djokic D, Redzic D, Aleksic D, Parezanovic M, Pasic S. Secondary hemophagocytic lymphohistiocytosis in a child with Leptospira infection: A case report. Turk J Pediatr 2018; 60: 735-738.

Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders.

Background: Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT).

Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation.

Background: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients.

Objectives: We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT.

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.

International Nosocomial Infection Control Consortium (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module.

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S.

The role of D-dimer in prediction of the course and outcome in pediatric acute pancreatitis.

Background: Current predictive severity scores for pediatric acute pancreatitis are either extrapolated from adult studies or difficult to use in practice. The aim of this study was to assess the value of the plasma D-dimer level as a marker of severity and outcome in pediatric AP.

Methods: 36 patients (aged 1-17 yrs) with AP were included in the study.

Health-related quality of life, anxiety, and depressive symptoms in children with primary immunodeficiencies.

Introduction: The aims of this study were to evaluate levels of health-related quality of life (HRQOL) and the presence of anxiety and depressive symptoms in children with primary immunodeficiency disease (PID) in Serbia.

Materials And Methods: Self- and parent-rated data from 25 children with PID were available. As controls, data from 50 children with juvenile idiopathic arthritis (JIA) and 89 healthy children were included.

Severe combined immunodeficiency in Serbia and Montenegro between years 1986 and 2010: a single-center experience.

Severe combined immunodeficiency (SCID), including the 'variant' Omenn syndrome (OS), represent a heterogeneous group of monogenic disorders characterized by defect in differentiation of T- and/or B lymphocytes and susceptibility to infections since birth. In the period of 25 years, between January 1986 and December 2010, a total of 21 patients (15 SCID, 6 OS) were diagnosed in Mother & Child Health Institute of Serbia, a tertiary-care teaching University hospital and a national referral center for patients affected with primary immunodeficiency (PID). The diagnoses were based on anamnestic data, clinical findings, and immunological and genetic analysis.

Central nervous system involvement in hemophagocytic lymphohistiocytosis: a single-center experience.

Background: Hemophagocytic lymphohistiocytosis is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system.

Patients And Methods: Thirty children diagnosed with hemophagocytic lymphohistiocytosis between 1997 and 2010 were reviewed and analyzed. Central nervous system disease involvement was defined as the presence of neurological symptoms and signs or elevated values of cerebrospinal fluid cells and/or proteins.

Nijmegen breakage syndrome and chronic polyarthritis.

We report on pediatric patient with Nijmegen breakage syndrome (NBS), a rare DNA repair disorder characterized by microcephaly, immunodeficiency and predisposition to malignant lymphomas, who developed juvenile idiopathic arthritis (JIA)-like polyarthritis. In patients with primary immunodeficiencies (PID), septic arthritis due to pyogenic bacteria or mycoplasmal arthritis are the most common osteoarticular manifestations. In certain PID, chronic, non-infectious arthritis resembling rheumatoid arthritis may occur.

Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency.

In immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother.

Therapeutic approaches for the treatment of renal disease in juvenile systemic lupus erythematosus: an international multicentre PRINTO study.

Objectives: To evaluate therapeutic approaches and response to therapy in juvenile systemic lupus erythematosus (SLE) with renal involvement in a large prospective international cohort from four geographic areas.

Methods: New onset and flared patients with active renal disease (proteinuria ≥0.5 g/24 h) were enrolled in 2001-2004.