Analysis of Functional Cis-regulatory Elements Reveals Novel Transcriptional Regulatory Mechanisms in Gonadal Development.

Recent studies have demonstrated that the production of bidirectional enhancer-derived transcripts (eRNAs) is a characteristic of an active Cis-regulatory element (CRE). Higher levels of eRNA synthesis correlate with the activation of histone modifications, a potentially valuable tool for deciphering the complexity of the gene regulatory network. To understand the changes of CREs during gonadal development in mice, we collected gonadal WT1-positive cells from the piggyBac-Wt1-mCherry-2A-EGFP (PBWt1-RG) reporter strain at E13.

Effect of Epstein-Barr Virus infection on gene regulation in immune cells of patients with Immune-Mediated Diseases.

It has been known that Epstein-Barr virus (EBV) can latently infect immune cells after the initial infection, and epidemiological studies have suggested its association with the onset of immune-mediated diseases (IMDs). However, the specific impact of EBV infection on IMDs pathology remains unclear. We quantified EBV load of B cell subsets (Naïve B cells, Unswitched memory B cells, Switched memory B cells, Double negative B cells, and Plasmablasts) in IMD patients as well as healthy control (HC) using bulk RNA sequencing data of 504 donors.

Real-world experience of tixagevimab/cilgavimab prophylaxis in Japanese patients with immunodeficiency.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe illness and mortality in patients with immunodeficiency. Although vaccination has been recommended, the induction of protective antibodies by immunization, and thus the disease-preventive effect, has proven insufficient in immunodeficient patients, especially in those with predominantly antibody deficiency. A monoclonal antibody combination of tixagevimab and cilgavimab (TIX/CIL) was developed as a pre-exposure prophylaxis (PrEP).

Prolonged diagnostic journey in delayed-onset adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency typically presents as a severe combined immunodeficiency in early infancy, although its onset may be delayed in some cases. We encountered two patients diagnosed with ADA deficiency in adulthood. In addition to previously reported cases, we aimed to identify and characterize the clinical and immunological features associated with delayed- and late-onset ADA deficiency.

A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development.

Genetic studies in mice have shown that the zinc finger transcription factor BCL11B has an essential role in regulating early T cell development and neurogenesis. A de novo heterozygous missense BCL11B variant, BCL11B, was isolated from a patient with T cell deficiency and neurological disorders. Here, we show that mice harboring the corresponding Bcl11b mutation show the emergence of natural killer (NK)/group 1 innate lymphoid cell (ILC1)-like NKp46 cells in the thymus and reduction in TBR1 neurons in the neocortex, which are observed with loss of Bcl11a but not Bcl11b.

A Non-targeted Proteomics Newborn Screening Platform for Inborn Errors of Immunity.

Purpose: Newborn screening using dried blood spot (DBS) samples for the targeted measurement of metabolites and nucleic acids has made a substantial contribution to public healthcare by facilitating the detection of neonates with genetic disorders. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for inborn errors of immunity (IEIs).

Methods: DBS samples from 40 healthy newborns and eight healthy adults were subjected to non-targeted proteomics analysis using liquid chromatography-mass spectrometry after removal of the hydrophilic fraction.

Familial and early recurrent pheochromocytoma in a child with a novel in-frame duplication variant of .

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors often linked to underlying genetic variants. Genetic analysis can promote gene-adjusted, specific follow-up, and surveillance protocols for both patients and their families at risk. We report the case of a 7-yr-old boy with bilateral pheochromocytoma, which recurred a year after partial adrenalectomy.

A case of primary ciliary dyskinesis with DRC1 deletion and literature review: Additional evidence on the founder effect.

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disease caused by defects in various genes affecting ciliary function. It is currently unclear why DRC1 gene variants are a relatively frequent cause of disease in Japanese and Korean patients.

Methods: A 12-year-old Japanese girl with bronchiectasis was suspected of PCD and examined using whole-exome sequencing (WES).

Discordant Phenotypes of Nephritis in Patients with X-linked Agammaglobulinemia.

Purpose: To define the clinical and histological characteristics of nephritis in patients with X-linked agammaglobulinemia (XLA) and their immunological profiles.

Methods: The clinical, immunological, and histological findings of nine patients with XLA and nephritis were retrospectively analyzed.

Results: Based on kidney histological findings, patients with XLA and nephritis could be divided into two groups, viz.

Case Report: A neonatal case of cryopyrin-associated periodic syndrome with severe funisitis and neonatal asphyxia.

Cryopyrin-associated periodic syndrome (CAPS) is a genetic disorder and autoinflammatory disease characterized by chronic inflammation throughout the body. The most severe form of CAPS, Chronic Infantile Neurologic Cutaneous, and Articular (CINCA) syndrome, also known as Neonatal Onset Multisystem Inflammatory Disease (NOMID), has three main features: skin rash, CNS involvement, and joint symptoms. Although these symptoms are typically reported shortly after birth, there have been a few reports of prenatal inflammation.

AIOLOS-Associated Inborn Errors of Immunity.

AIOLOS, encoded by the IKZF3 gene, belongs to the Ikaros zinc finger transcription factor family and plays a pivotal role in regulating lymphocyte development. Recently, heterozygous missense loss-of-function variants within the DNA-binding domain of the IKZF3 gene (G159R, N160S, and G191R) have been identified in patients with inborn errors of immunity (IEI). Additionally, a missense and a truncating variant (E82K and Q402X) leading to the AIOLOS haploinsufficiency have been documented.

Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity.

Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited. We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months.

Exploring viral infections' role in Kawasaki disease onset: A study during the COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, known viral diseases declined in all ages. By using the current situation as a natural experiment, this study aimed to evaluate whether the change in the incidence of Kawasaki disease (KD) during the COVID-19 pandemic varies with age and whether a specific infectious disease mediates the occurrence of KD. Monthly number of KD patients were extracted from the nationwide inpatient database.

Intracranial residual lesions following early intensification in a patient with T-cell acute lymphoblastic leukemia: a case report.

Background: T-cell acute lymphoblastic leukemia (T-ALL) tends to involve central nervous system (CNS) infiltration at diagnosis. However, cases of residual CNS lesions detected at the end of induction and post early intensification have not been recorded in patients with T-ALL. Also, the ratio and prognosis of patients with residual intracranial lesions have not been defined.

Stage III Chorioamnionitis is Associated with Reduced Risk of Severe Retinopathy of Prematurity.

Objective: To identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP).

Study Design: We retrospectively analyzed 2 different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks' gestation (January 2003 through April 2021, n = 38 013).

Clinical and molecular significance of flow cytometric analysis for reactive oxygen species production and residual p67 expression in p67-deficient chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by molecular defects in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. p67-CGD is an autosomal recessive CGD, which is caused by a defect in the cytosolic components of NADPH oxidase, p67, encoded by NCF2. We previously established a flow cytometric analysis for p67 expression, which allows accurate assessment of residual protein expression in p67-CGD.