EZH2-dependent epigenetic reprogramming in the central nucleus of amygdala regulates adult anxiety in both sexes after adolescent alcohol exposure.

Alcohol use and anxiety disorders occur in both males and females, but despite sharing similar presentation and classical symptoms, the prevalence of alcohol use disorder (AUD) is lower in females. While anxiety is a symptom and comorbidity shared by both sexes, the common underlying mechanism that leads to AUD and the subsequent development of anxiety is still understudied. Using a rodent model of adolescent intermittent ethanol (AIE) exposure in both sexes, we investigated the epigenetic mechanism mediated by enhancer of zeste 2 (EZH2), a histone methyltransferase, in regulating both the expression of activity-regulated cytoskeleton-associated protein (Arc) and an anxiety-like phenotype in adulthood.

Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis.

Objective: To evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH) genes and systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS).

Methods: Targeted sequencing of HLH genes (, , , , , ) was performed in sJIA subjects from an established cohort. Sequence data from control subjects were obtained (dbGaP:phs000280.

Shared genomic segments analysis identifies MHC class I and class III molecules as genetic risk factors for juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease encompassing several clinically defined subtypes of varying severity. The etiology of JIA remains largely unknown, but genome-wide association studies (GWASs) have identified up to 22 genes associated with JIA susceptibility, including a well-established association with HLA-DRB1. Continued investigation of heritable risk factors has been hindered by disease heterogeneity and low disease prevalence.

Safety and effectiveness of abatacept in juvenile idiopathic arthritis: results from the PRINTO/PRCSG registry.

Objective: The aim of this study was to report the interim 5-year safety and effectiveness of abatacept in patients with JIA in the PRINTO/PRCSG registry.

Methods: The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept.

Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia at Multiple Centers.

Background: Patients with partial DiGeorge syndrome (pDGS) can present with immune dysregulation, the most common being autoimmune cytopenia (AIC). There is a lack of consensus on the approach to type, combination, and timing of therapies for AIC in pDGS. Recognition of immune dysregulation early in pDGS clinical course may help individualize treatment and prevent adverse outcomes from chronic immune dysregulation.

Prevalence of tissue transglutaminase antibodies and IgA deficiency are not increased in juvenile idiopathic arthritis: a case-control study.

Background: The prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1-7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA.

Divergent Population-Specific Effects of Chronic Ethanol Exposure on Excitability and Inhibitory Transmission in Male and Female Rat Central Amygdala.

The central nucleus of the amygdala (CeA) is implicated in alcohol use disorder (AUD) and AUD-associated plasticity. The CeA is a primarily GABAergic nucleus that is subdivided into lateral and medial compartments with genetically diverse subpopulations. GABA receptors are heteromeric pentamers with subunits conferring distinct physiological characteristics.

Abatacept as Monotherapy and in Combination With Methotrexate in Patients With Juvenile Idiopathic Arthritis: Analysis of 2 Phase III Trials.

Objective: To describe the efficacy and safety data of children with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with abatacept (ABA) + methotrexate (MTX) or ABA monotherapy when prior MTX use was either ineffective or not tolerated.

Methods: Posthoc analysis of 2 phase III trials of subcutaneous (SC) and intravenous (IV) ABA over 2 years in patients with pcJIA (aged 2-17 years). Patients were stratified by treatment with ABA + MTX or ABA monotherapy and further by prior biologic use.

Case report: Novel variants in RELA associated with familial Behcet's-like disease.

RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery.

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.

Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.

Methods: We identified 191 patients from 33 countries with 72 unique mutations.

Unraveling the epigenomic and transcriptomic interplay during alcohol-induced anxiolysis.

Positive effects of alcohol drinking such as anxiolysis and euphoria appear to be a crucial factor in the initiation and maintenance of alcohol use disorder (AUD). However, the mechanisms that lead from chromatin reorganization to transcriptomic changes after acute ethanol exposure remain unknown. Here, we used Assay for Transposase-Accessible Chromatin followed by high throughput sequencing (ATAC-seq) and RNA-seq to investigate epigenomic and transcriptomic changes that underlie anxiolytic effects of acute ethanol using an animal model.

Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure.

Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. Adolescent alcohol exposure induces epigenetic reprogramming at the enhancer region of the activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as synaptic activity response element (SARE), and decreases expression in the amygdala of both rodents and humans. The causal role of amygdalar epigenomic regulation at SARE in adult anxiety and drinking after adolescent alcohol exposure is unknown.

Lymphoma in Partial DiGeorge Syndrome: Report of 2 Cases.

Primary immunodeficiency diseases are associated with an increased tendency for noninfectious complications of autoimmunity and malignancy, particularly leukemia and lymphoma. The mechanisms of immune dysregulation have been linked to the combination of dysregulated immune cells and environmental factors such as infections. In particular, dysfunction in T-cell subsets and Epstein-Barr virus contributes to the development of autoimmunity and lymphoproliferative disease in primary immunodeficiency diseases.

A novel transition clinic structure for adolescent and young adult patients with childhood onset rheumatic disease improves transition outcomes.

Background: The transition of health care from Pediatric to Adult providers for adolescents and young adults with chronic disease is associated with poor outcomes. Despite the importance of this transition, over 80% of these patients do not receive the services necessary to transition to Adult health care. In 2018, we initiated a transition clinic structure, integrating an Internal Medicine - Pediatrics trained Adult Rheumatologist in a Pediatric Rheumatology clinic to guide this transition.

Multiple Cranial Neuropathies and Pachymeningitis in a Patient With a Pathogenic Nucleotide-Binding Oligomerization Domain 2 Polymorphism.

An 11-year-old boy presented with 2 weeks of intermittent headache, right orbital pain, and constant diplopia. Brain MRI showed dural thickening and enhancement of the right lateral cavernous sinus, right orbital apex, and tentorium. Initial cerebral spinal fluid analysis showed only mild pleocytosis, and serum diagnostics were unrevealing.

Current and Future Perspectives of Noncoding RNAs in Brain Function and Neuropsychiatric Disease.

Noncoding RNAs (ncRNAs) represent the majority of the transcriptome and play important roles in regulating neuronal functions. ncRNAs are exceptionally diverse in both structure and function and include enhancer RNAs, long ncRNAs, and microRNAs, all of which demonstrate specific temporal and regional expression in the brain. Here, we review recent studies demonstrating that ncRNAs modulate chromatin structure, act as chaperone molecules, and contribute to synaptic remodeling and behavior.

Histone modifications, DNA methylation, and the epigenetic code of alcohol use disorder.

Alcohol use disorder (AUD) is a leading cause of morbidity and mortality. Despite AUD's substantial contributions to lost economic productivity and quality of life, there are only a limited number of approved drugs for treatment of AUD in the United States. This chapter will update progress made on the epigenetic basis of AUD, with particular focus on histone post-translational modifications and DNA methylation and how these two epigenetic mechanisms interact to contribute to neuroadaptive processes leading to initiation, maintenance and progression of AUD pathophysiology.

Variability in Interpretation of Magnetic Resonance Imaging of the Pediatric Sacroiliac Joint.

Objective: Magnetic resonance imaging (MRI) is pivotal in the assessment of early sacroiliitis in children. We aimed to evaluate the agreement between local radiology reports and central imaging reviewers for active inflammation and structural damage at the sacroiliac (SI) joints.

Methods: Eight hospitals each contributed up to 20 cases of consecutively imaged children and adolescents with juvenile idiopathic arthritis and suspected sacroiliitis.

Alcohol Makes Its Epigenetic Marks.

The toxic effects of alcohol consumption are dependent upon its metabolism in the liver to downstream metabolites: acetaldehyde, acetate, and acetyl-CoA. Recently, in Nature, Mews et al. (2019) have discovered that acetyl-CoA derived from alcohol plays an important epigenetic role in regulating ethanol's effects on the brain through histone acetylation.