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.

Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response.

Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing.

Peripheral blood cells RNA-seq identifies differentially expressed gene network linked to lymphocyte subsets alterations and active lupus nephritis associated with declines in renal function.

Background: The aim of this study was to investigate whether quantitative changes in lymphocyte subsets and gene expression in peripheral blood (PB) cells are related to the clinical manifestations and pathogenesis of lupus nephritis (LN).

Methods: We enrolled 95 pediatric-onset SLE patients with renal involvement who presented with 450 clinical episodes suspicious for LN flare. Percentages of lymphocyte subsets at each episode were determined.

Rituximab as an effective add-on maintenance therapy for disease activities in childhood-onset systemic lupus erythematosus.

Objectives: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can result in high morbidity if not treated. This retrospective study aimed to evaluate the outcomes of rituximab treatment in a paediatric SLE cohort in Taiwan.

Methods: The medical records of paediatric patients diagnosed with SLE at the National Taiwan University Hospital between January 1992 and August 2022 who received rituximab as maintenance therapy between January 2015 and August 2022 were retrospectively reviewed.

Respiratory-syncytial virus immunoprophylaxis on asthma symptoms development in prematurity with bronchopulmonary dysplasia.

Background: Infants with respiratory-syncytial virus bronchiolitis hospitalization are more likely to develop wheezing and subsequent asthma. Reportedly, palivizumab prophylaxis effectively prevents respiratory-syncytial virus hospitalization in high-risk children-such as premature infants or infants with bronchopulmonary dysplasia (BPD).

Objective: We sought to explore the effect of respiratory-syncytial virus immunoprophylaxis on the risk of asthma development in premature infants with BPD in subtropical areas.

Differentially expressed microRNAs in peripheral blood cell are associated with downregulated expression of IgE in nonallergic childhood asthma.

Childhood asthma is a heterogeneous disease characterized by chronic airway inflammation, leading to a broad range of clinical presentations. Nonallergic asthma is asthma without allergic sensitization. Both clinical manifestations and immunopathological mechanisms of nonallergic childhood asthma were rarely investigated.

Risk factors for subsequent lupus nephritis in patients with juvenile-onset systemic lupus erythematosus: a retrospective cohort study.

Background: Lupus nephritis (LN) is a crucial organ involvement in systemic lupus erythematosus (SLE). Patients with LN have higher morbidity and mortality rates than those without. Among all patients with LN, 20-40% had delayed onset, but the data for patients with juvenile-onset SLE (jSLE), who have a higher percentage of LN than patients with adult-onset SLE (aSLE), were limited.

A missense variant in the nuclear localization signal of DKC1 causes Hoyeraal-Hreidarsson syndrome.

Hoyeraal-Hreidarsson syndrome (HHS) is the most severe form of dyskeratosis congenita (DC) and is caused by mutations in genes involved in telomere maintenance. Here, we identified male siblings from a family with HHS carrying a hemizygous mutation (c.1345C > G, p.

Clinical, laboratory characteristics and growth outcomes of children with growing pains.

Growing pains (GP), a common and benign pain syndrome of unknown etiology, is characterized by bilateral recurrent leg pain in childhood. There are no standardized diagnostic criteria for GP, and the diagnosis is often made by exclusion. To identify clinical and laboratory features, we included patients < 12 years with GP at National Taiwan University Children's Hospital between April 2006 and April 2019 in a retrospective study.

Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa.

Clinical features and outcomes of patients with chronic granulomatous disease in Taiwan.

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by defective neutrophil killing of microbial pathogens and recurrent infections. We aimed to investigate the clinical, genetic features, treatment, and outcomes in patients with CGD.

Methods: Pediatric patients diagnosed with CGD from a medical center in Taiwan were enrolled from January 1999 to Oct 2021.

Taiwan guidelines for the diagnosis and management of pediatric atopic dermatitis: Consensus statement of the Taiwan Academy of Pediatric Allergy, Asthma and Immunology.

Atopic dermatitis (also known as atopic eczema) is a chronic relapsing inflammatory skin disease commonly seen in children, with increasing prevalence over the past few decades in many countries including Taiwan. The management of pediatric atopic dermatitis can be challenging, particularly as treatment options are expanding with the emergence of novel systemic and topical anti-inflammatory medications in recent years. The Taiwan Academy of Pediatric Allergy, Asthma and Immunology (TAPAAI) has developed the Taiwan guidelines for the diagnosis and management of pediatric atopic dermatitis, which provides a concise overview of its epidemiology, clinical characteristics and diagnosis, mechanisms, treatments, and education.

Predictive characteristics to discriminate the longitudinal outcomes of childhood asthma: a retrospective program-based study.

Background: Childhood asthma is an inflammatory disease with heterogeneous outcomes. We sought to determine the impact of total IgE, blood eosinophil, allergen sensitization, and inhaled corticosteroid (ICS) on longitudinal outcomes and to identify characteristics for discriminating different outcomes.

Methods: We conducted a retrospective study in 383 childhood asthma patients and another 313 patients with blood eosinophil data only receiving regular program-based visits from September 1, 2004, to December 31, 2018.

CTLA-4 gene mutation and multiple sclerosis: A case report and literature review.

We reported a patient with autoimmunity (multiple sclerosis), immunodeficiency (hypogammaglobulinemia with severe infections), enteropathy (diarrhea with intestinal inflammation), splenomegaly, lymphadenopathy and lymphocytic infiltration of non-lymphoid organs (lung, gut and brain). The patient was found to have a heterozygous mutation in cytotoxic T lymphocyte antigen-4, and had excellent response to abatacept.

Differential parameters between activity flare and acute infection in pediatric patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) patients are vulnerable to infections. We aim to explore the approach to differentiate active infection from disease activity in pediatric SLE patients. Fifty pediatric SLE patients presenting with 185 clinical visits were collected.

Chronic Granulomatous Disease: a Comprehensive Review.

Chronic granulomatous disease (CGD) is a primary immunodeficiency of phagocyte function due to defective NADPH oxidase (phox). Compared with the common types of CYBB/gp91, NCF1/p47, and CYBA/p22 deficiency, NCF4/p40 deficiency is a mild and atypical form of CGD without invasive bacterial or fungal infections. It can be diagnosed using serum-opsonized E.

Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency.

Background: Mutations in the recombinase-activating genes cause severe immunodeficiency, with a spectrum of phenotypes ranging from severe combined immunodeficiency to immune dysregulation. Hematopoietic stem cell transplantation is the only curative option, but a high risk of graft failure and poor immune reconstitution have been observed in the absence of myeloablation.

Objectives: Our aim was to improve multilineage engraftment; we tested nongenotoxic conditioning with anti-CD45 mAbs conjugated with saporin CD45 (CD45-SAP).

Tai Chi Chuan Exercise Improves Lung Function and Asthma Control through Immune Regulation in Childhood Asthma.

Background: Tai Chi Chuan (TCC) is an exercise of low to moderate intensity with key features of mindfulness, structural alignment, and flexibility to relax the body and mind in adults. Our previous study showed that TCC could improve the quality of life (QoL), pulmonary function, and fractional exhaled nitric oxide in asthmatic children. We further investigated whether the benefits induced by TCC were associated with immune regulation.