Altered Purinergic Signaling and CD8+ T Cell Dysregulation in STAT3 GOF Syndrome.

Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants in STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, and immune dysregulation. In both primary human and mouse models of STAT3 GOF, CD8+ T cells have been implicated as pathogenic drivers of autoimmunity.

Leveraging Systems Immunology to Optimize Diagnosis and Treatment of Inborn Errors of Immunity.

Inborn errors of immunity (IEI) are monogenic disorders that can cause diverse symptoms, including recurrent infections, autoimmunity and malignancy. While many factors have contributed, the increased availability of next-generation sequencing has been central in the remarkable increase in identification of novel monogenic IEI over the past years. Throughout this phase of disease discovery, it has also become evident that a given gene variant does not always yield a consistent phenotype, while variants in seemingly disparate genes can lead to similar clinical presentations.

Long-Term Outcomes and Health-Related Quality of Life in a Swiss Patient Group with Esophageal Atresia.

Introduction:  Surgical treatment of esophageal atresia (EA) has markedly improved, allowing the focus to shift from short-term complications and mortality to long-term complications and quality of life. Health-related quality of life (HRQoL) is variable and reported to range from reduced to unimpaired in patients with repaired EA. We assessed the HRQoL, determined the prevalence of long-term complications and their possible impact on the HRQoL in patients who had correction of EA in Switzerland.

Patterns of Immune Dysregulation in Primary Immunodeficiencies: A Systematic Review.

Background: Immune dysregulation is as important as susceptibility to infection in defining primary immunodeficiencies (PIDs). Because of the variability and nonspecificity of the symptoms of PIDs, diagnosis can be delayed-especially if a patient presents with immune dysregulation. Diagnosis is then based on certain combinations of symptoms and relies on the clinician's ability to recognize a pattern.