Patient-Reported Outcomes and Medical Provider Satisfaction Among Adult and Pediatric Ataxia-Telangiectasia Patients.

Purpose: Ataxia-telangiectasia (A-T) is a rare genetic condition with malfunctioning DNA repair processes resulting in significant clinical findings, including progressive neurologic decline, elevated malignancy risk, immunodeficiency, oculocutaneous telangiectasias, and severe pulmonary disease. Research has been limited into the quality of life of such patients and yet to be completed are studies quantitatively analyzing psychosocial, physical, and cognitive patient-reported outcomes (PROs) within the A-T population.

Methods: PRO evaluations of 90 international adult and pediatric A-T patients and their caregivers were completed via secure online administration of Patient-Reported Outcomes Measurement Information System (PROMIS) short forms evaluating anger, cognition, mood, social health, fatigue, pain, anxiety, and upper extremity function.

NF-κB and Related Autoimmune and Autoinflammatory Diseases.

The NF-κB pathway is a cardinal signaling pathway that has been implicated in the development of a diverse range of clinical diseases. Numerous cellular processes converge on this pathway, which results in cell proliferation and survival. Defects in this pathway and in its upstream regulators have been described as causing immunodeficiency.

In cis "benign" SOCS1 variants linked to enhanced interferon signaling and autoimmunity.

We aimed to characterize the genetic basis of disease in a family with multiple autoimmune manifestations, including systemic lupus erythematosus (SLE), immune thrombocytopenia, and autoimmune thyroiditis. Whole exome sequencing (WES) was conducted to identify candidate variants, which were analyzed by flow cytometry, immunoblotting, immunoprecipitation, and luciferase reporter assay in transfected 293T cells. Gene expression in peripheral blood mononuclear cells (PBMC) was profiled by bulk RNA sequencing and plasma cytokines were measured by proximity extension assay.

Newborn tandem mass spectroscopy screening for adenosine deaminase deficiency.

Background: Newborn screening (NBS) by means of T cell receptor excision circles (TREC) is now universal in the United States, Puerto Rico, and the Navajo Nation as a strategy to identify severe combined immunodeficiency (SCID) in newborns. Owing to the characteristics of adenosine deaminase (ADA) deficiency, a small but important number of cases can be missed by this screening.

Objective: To evaluate the results of the first year statewide NBS for ADA by means of dried blood spot NBS.

Case Report: Use of Obinutuzumab as an Alternative Monoclonal Anti-CD20 Antibody in a Patient With Refractory Immune Thrombocytopenia Complicated by Rituximab-Induced Serum Sickness and Anti-Rituximab Antibodies.

Management of refractory immune thrombocytopenia frequently involves rituximab, a chimeric anti-CD20 monoclonal antibody, to target B cells and induce remission in most patients. However, neutralizing antibodies to rituximab that nullify therapeutic response and may lead to serum sickness have been rarely reported. Here, we present a case of a young adult woman with Evans syndrome treated with rituximab, complicated by the development of serum sickness, acute respiratory distress syndrome, and platelet refractoriness presumed secondary to neutralizing antibodies to rituximab.

Immune Suppression in Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for high-risk hematologic disorders. There are multiple immune-mediated complications following allo-HSCT that are prevented and/or treated by immunosuppressive agents. Principal among these immune-mediated complications is acute graft-versus-host disease (aGVHD), which occurs when the new donor immune system targets host tissue antigens.

Elevated inflammatory responses and targeted therapeutic intervention in a preclinical mouse model of ataxia-telangiectasia lung disease.

Ataxia-telangiectasia (A-T) is an autosomal recessive, multisystem disorder characterized by cerebellar degeneration, cancer predisposition, and immune system defects. A major cause of mortality in A-T patients is severe pulmonary disease; however, the underlying causes of the lung complications are poorly understood, and there are currently no curative therapeutic interventions. In this study, we examined the lung phenotypes caused by ATM-deficient immune cells using a mouse model of A-T pulmonary disease.

Quality of life and patient-reported outcomes in chronic severe neutropenia conditions.

Quality of life (QOL) and patient-reported outcomes (PROs) assessments in immunodeficiency patients, including those with chronic severe neutropenia conditions, are imperative to determining modifiable health-related features to optimize care. We present the largest study to date of QOL in those with chronic severe neutropenia conditions with further evaluation of patient provider satisfaction and patient-reported outcome measures. Subjects completed electronic surveys assessing QOL, PROs, and patient provider satisfaction.

Neutropenia Is an Underrecognized Finding in Pediatric Primary Immunodeficiency Diseases: An Analysis of the United States Immunodeficiency Network Registry.

Background: The frequency of neutropenia in pediatric primary immunodeficiency disorders (PIDDs) is unknown and potentially underappreciated. Our study aimed to determine the overall frequency and severity of neutropenia in children diagnosed with a PIDD entered in the United States Immunodeficiency Network (USIDNET) patient registry.

Procedure: Neutropenia data and demographic/clinical information from 1145 patients younger than 21 years of age was obtained from the USIDNET registry.

Line Associated Thrombosis in Pediatric Patients With NF-κB Pathway Variants.

Our report explores the complex role that nuclear factor-kappa B (NF-κB) plays in thrombosis formation, inflammation, and immunity; while additionally demonstrating that patients with NF-κB pathway pathogenic variants appear to carry a substantial thrombotic risk, particularly when secondary thrombotic risk factors are present. We propose that prophylactic anticoagulation should be strongly considered in such patients during high-risk situations and provide additional hematologic management strategies for those with NF-κB pathway alterations. We hope our work also calls to attention the potential need for a broader assessment of venous thromboembolism risk in patients with immune dysregulation to better delineate which patient populations may benefit from anticoagulation prophylaxis.

KRAS mutant tenosynovial giant cell tumor in a pediatric patient: a case report.

Tenosynovial giant cell tumors (TSGCT) are a group of rare, benign soft tissue tumors with common histologic and cytogenetic features, with a median age of diagnosis being 47 years. Generally divided into localized and diffuse subtypes, TSGCTs are typically driven by overexpression of macrophage colony stimulating factor receptor-1 (CSF1R). Treatment of TSGCT is tumor resection, followed by radiation therapy in cases of incomplete resection.

Provider Perceptions of Quality of Life, Neurocognition, Physical Well-being, and Psychosocial Health in Patients with Primary Immunodeficiency/Immune Dysregulation Conditions.

Purpose: Both pediatric and adult patients with a primary immunodeficiency/immune dysregulation (PID/PIDR) diagnosis report inferior quality of life (QOL) and patient-reported outcomes (PROs) as compared with their healthy peers. Recognition of the negative impact on QOL and PROs provides an opportunity for clinicians to intervene with supportive measures. However, provider perceptions of PID/PIDR patients' quality of life, physical well-being, psychosocial health and neurocognition, and access to supportive resources have yet to be systematically evaluated.

Immune-Mediated Cytopenias After Hematopoietic Cell Transplantation: Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment Strategies.

Purpose Of Review: Discuss the pathophysiology, clinical presentation, diagnosis, and treatment of immune-mediated cytopenias (IMC) after hematopoietic cell transplantation (HCT).

Recent Findings: Key risk factors for post-HCT IMC include younger age, non-malignant disease, and umbilical cord blood stem cell source. While anemia predominates, any or all three hematopoietic cell lines can be affected.

Severe Combined Immunodeficiency: A Review for Neonatal Clinicians.

The proper development and function of T cells is imperative in the creation of adequate cell-mediated and humoral immunity. Healthy term newborns have baseline immune immaturity, increasing their risk of infections, but significant immunologic consequences can occur, because of abnormal T-cell maturation. Combined immunodeficiencies can result, because B cells and natural killer cells rely on successful interactions with T cells to ensure their proper performance and survival.