Transition-related outcomes among a cohort of patients with juvenile idiopathic arthritis.

A major goal in juvenile idiopathic arthritis (JIA) long-term management is to ensure a successful transition to adult age. This study aims to assess transition outcomes in a group of JIA patients during their passage from pediatric to adult healthcare assistance at a single center. This is a cross-sectional study.

In-Depth Phenotyping of -Related Disease and Its Role in 17q12 Genomic Disorder.

Glycosylphosphatidylinositol (GPI) biosynthesis defect 11 (GPIBD11), part of the heterogeneous group of congenital disorders of glycosylation, is caused by biallelic pathogenic variants in . This rare disorder has previously been described in only 12 patients. We report four novel patients: two sib fetuses with congenital anomalies affecting several organs, including the heart; a living girl with tetralogy of Fallot, global developmental delay, behavioral abnormalities, and atypic electroencephalography (EEG) without epilepsy; a girl with early-onset, treatment-resistant seizures, developmental regression, and recurrent infections, that ultimately passed away prematurely due to pneumonia.

Report of the Italian Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome in the Target Therapy Era.

Background: Activated Phosphoinositide 3-Kinase (PI3K) δ Syndrome (APDS), an inborn error of immunity due to upregulation of the PI3K pathway, leads to recurrent infections and immune dysregulation (lymphoproliferation and autoimmunity).

Methods: Clinical and genetic data of 28 APDS patients from 25 unrelated families were collected from fifteen Italian centers.

Results: Patients were genetically confirmed with APDS-1 (n = 20) or APDS-2 (n = 8), with pathogenic mutations in the PIK3CD or PIK3R1 genes.

Does It Run in Your Family? Inherited Truncating PSMD12 Variants Broaden the Phenotypic Spectrum of Stankiewicz-Isidor Syndrome.

Alteration in the ubiquitin-proteasome system results in human disorders with neurological and/or autoinflammatory presentation. Haploinsufficiency of PSMD12, which encodes a subunit of the core component of the proteasome, causes Stankiewicz-Isidor syndrome (STISS), characterized by intellectual disability, autism spectrum disorder, craniofacial dysmorphisms, with or without other congenital anomalies, and autoinflammation. We described six patients (four adults) from two unrelated families carrying a known p.

Consensus of the Italian Primary Immunodeficiency Network on the use and interpretation of genetic testing for the diagnosis of inborn errors of immunity (IEI).

Background: Inborn errors of immunity (IEIs) are more than 500 different rare congenital disorders of the immune system characterized by susceptibility to infections and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High throughput sequencing techniques may allow a timely genetic definition.

Interleukin-1 blockade in patients with Wiskott-Aldrich syndrome: a retrospective multinational case series.

Up to 70% of patients with Wiskott-Aldrich syndrome (WAS) develop autoimmune and inflammatory manifestations. Dysregulation of interleukin 1 (IL-1) may be involved in their pathogenesis, yet there is little evidence on treatment with anti-IL-1 agents in these patients. We conducted a multicenter retrospective analysis of 9 patients with WAS treated with anti-IL-1 agents (anakinra or canakinumab).

Siglec-1, an easy and contributory inflammation marker in rheumatology.

Objectives: Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are poorly informative about interferon (IFN)-related disorders. In these conditions, the measure of the interferon score (IS), obtained by measuring the expression of IFN-stimulated genes, has been proposed. Flow cytometry-based assays measuring sialic-acid-binding Ig-like lectin 1 (Siglec-1) expression could be a more practical tool for evaluating IFN-inflammation.

An easy assay to detect autoantibodies neutralizing cytokines in subjects with critical infections.

Autoantibodies against type I interferon (IFN) are associated with a worse outcome in COVID-19. The measurement of cytokine-neutralizing autoantibodies has been limited, hindering understanding of their role in clinical practice. We showed that an easy and reliable assay can be reproduced and validated to measure the neutralizing potency of autoantibodies directed to type I or type II IFN.

Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34 cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT.

Rheumatological complaints in H syndrome: from inflammatory profiling to target treatment in a case study.

Background: H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many of which are related to the immune-rheumatological field. These include scleroderma-like skin changes, deforming arthritis, and enlarged lymph nodes.

Erythropoietic protoporphyria: case reports for clinical and therapeutic hints.

Background: Erythropoietic protoporphyria is a rare disorder which represents an important health problem in children, causing painful photosensitivity. Little is known on the correlation between genetic profile and clinical manifestations. The standard of care for Erythropoietic protoporphyria is based on avoiding sun and using sun protections, but recent literature has suggested that cimetidine may have a role in improving sun sensitivity.

A very rare cause of pre-capillary pulmonary hypertension: The PAMI syndrome.

We report the first known case of PAMI syndrome associated with pulmonary arterial hypertension (PAH) with a positive response to cyclophosphamide and pulmonary vasodilators. The patient's history began at 7 months with severe pancytopenia and fever. As time progressed, migrating arthritis, hepatosplenomegaly, and a growth deficit manifested without a plausible explanation.

Subcutaneous tocilizumab in the management of non-infectious uveitis in children: a brief report.

Background: Tocilizumab is a humanized monoclonal antibody that acts as an IL-6 receptor antagonist. Intravenous tocilizumab is considered an option for children with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis. In contrast, the potential of subcutaneous drug use with this indication is more controversial.

A "SURFin' Leukemia": Acute Lymphoblastic Leukemia Masquerading as a Syndrome of Undifferentiated Recurrent Fever.

Periodic fever is not uncommon in childhood and is often ascribed to autoinflammatory conditions; however, it may be present also in children with cancer. We here describe the case of a 3-year-old boy with acute lymphoblastic leukemia who initially presented with a 4-month history of recurrent, stereotyped episodes of fever and localized joint pain, separated by completely symptom-free intervals. These symptoms were initially interpreted as a possible syndrome of undifferentiated recurrent fever until more signs of leukemia became apparent.

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.

Genetic bases of C7 deficiency: systematic review and report of a novel deletion determining functional hemizygosity.

Primary complement system (C) deficiencies are rare but notably associated with an increased risk of infections, autoimmunity, or immune disorders. Patients with terminal pathway C-deficiency have a 1,000- to 10,000-fold-higher risk of infections and should be therefore promptly identified to minimize the likelihood of further infections and to favor vaccination. In this paper, we performed a systematic review about clinical and genetic patterns of C7 deficiency starting from the case of a ten-year old boy infected by and with clinical presentation suggestive of reduced C activity.

Inborn Errors of Immunity in Children with Autoimmune and Allergic Complaints: A Single Center Experience from Diagnosis to Treatment.

Inborn errors of immunity (IEI) associated with immune dysregulation are not sufficiently addressed in shared recommendation, resulting in delayed diagnosis and high morbidity. The availability of precision medicine for some of these immune defects makes it urgent to evaluate effective strategies to diagnose and treat such defects before the occurrence of severe complications. A diagnosis of an IEI in these patients enabled the use of a more specific treatment in most cases, and these have the potential to prevent further disease progression.

Type I interferon signature as a possible new marker for stratification of patients with juvenile idiopathic arthritis.

Objectives: The interferon score (IS) quantifies the expression of interferon-stimulated genes in peripheral blood, providing an indirect estimate of interferon-mediated inflammation in rheumatological disorders. This study explores the clinical significance of IS among a cohort of patients affected by juvenile idiopathic arthritis (JIA) and its relevance to disease stratification and prognosis.

Methods: All patients referred to the Rheumatology Service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy, with a diagnosis of JIA (2001 ILAR criteria) were consecutively recruited.