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.

Diagnosis and classification of immune-mediated thrombocytopenia.

Immune thrombocytopenia, or ITP, has been recognized as a clinical entity for centuries, and the importance of humoral mechanisms in the pathophysiology of ITP has been recognized for decades. Despite the long history of the syndrome, progress in understanding its epidemiology and management has been hindered by inconsistencies in nomenclature and classification schema together with the inherent heterogeneity in characteristics of global populations and ITP-associated disorders. In the past decade, great strides have been made in devising a common language for caregivers and investigators alike through standardization definitions and outcome measures, while new tools have become available for management of its clinical manifestations.

Macrophage activation syndrome in autoimmune disease.

Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosis that is characteristically associated with autoimmune diatheses. The diagnosis of incipient MAS in patients with autoimmune disease requires a high index of suspicion, as several characteristics of the disorder may be present in the underlying condition or infectious complications associated with the treatment thereof.

The geoepidemiology of immune thrombocytopenic purpura.

First described in 1735 (Watson-Williams et al., 1958), immune-mediated platelet destruction is a phenomenon of protean associations that has historically varied in its definition. Recently, consensus guidelines were proposed for a standardized system of nomenclature that preserves the acronym "ITP" but encompasses a number of causes of immune-mediated thrombocytopenias, including both primary immune thrombocytopenia as well as such entities as thrombocytopenia associated with connective tissue diseases or cancer.

Common variable immunodeficiency: etiological and treatment issues.

One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID).

Allergic reactions to peanuts, tree nuts, and seeds aboard commercial airliners.

Background: Minimal data exist on the prevalence and characteristics of in-flight reactions to foods.

Objectives: To characterize reactions to foods experienced by passengers aboard commercial airplanes and to examine information about flying with a food allergy available from airlines.

Methods: Telephone questionnaires were administered to individuals in a peanut, tree nut, and seed allergy database who self-reported reactions aboard aircraft.

On reversing the persistence of memory: hematopoietic stem cell transplant for autoimmune disease in the first ten years.

There has been a remarkable history in the treatment of patients with autoimmune disease in the last century. Prior to the development of newer NSAIDs and corticosteroids, the care of patients with autoimmune disease was limited to aspirin and generally homeopathic therapies such as paraffin. In the last 30 years, the introduction and acceptance of cytotoxic drugs such as methotrexate and cyclophosphamide have greatly advanced the treatment of patients with severe autoimmune diseases.

Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice.

Cholesterol 7alpha-hydroxylase, a rate-limiting enzyme for bile acid synthesis, has been implicated in genetic susceptibility to atherosclerosis. The gene, CYP7A1, encoding a protein with this activity, is expressed normally only in hepatocytes and is highly regulated. Our cyp7A1 gene knockout mouse colony, as young adults on a chow diet, is hypercholesterolemic.