Who's your data? Primary immune deficiency differential diagnosis prediction via machine learning and data mining of the USIDNET registry.

Purpose: There are currently more than 480 primary immune deficiency (PID) diseases and about 7000 rare diseases that together afflict around 1 in every 17 humans. Computational aids based on data mining and machine learning might facilitate the diagnostic task by extracting rules from large datasets and making predictions when faced with new problem cases. In a proof-of-concept data mining study, we aimed to predict PID diagnoses using a supervised machine learning algorithm based on classification tree boosting.

Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry.

Rationale: Eosinophilic gastrointestinal disorders (EGID), including eosinophilic esophagitis (EoE), are inflammatory disorders of the gastrointestinal mucosa mediated by complex immune mechanisms. Although there have been initial reports of EGID in patients with inborn errors of immunity (IEI), little is known about the presentation of EGID in immunodeficient individuals.

Methods: We queried the U.

Evolution of Gene Therapy, Historical Perspective.

The earliest conceptual history of gene therapy began with the recognition of DNA as the transforming substance capable of changing the phenotypic character of a bacterium and then as the carrier of the genomic code. Early studies of oncogenic viruses that could insert into the mammalian genome led to the concept that these same viruses might be engineered to carry new genetic material into mammalian cells, including human hematopoietic stem cells (HSC). In addition to properly engineered vectors capable of efficient safe transduction of HSC, successful gene therapy required the development of efficient materials, methods, and equipment to procure, purify, and culture HSC.

Pulmonary Disease Burden in Primary Immune Deficiency Disorders: Data from USIDNET Registry.

Purpose: Pulmonary manifestations are common in patients with primary immunodeficiency disorders (PIDs) but the prevalence, specific diseases, and their patterns are not well characterized.

Methods: We conducted a retrospective analysis of pulmonary diseases reported in the database of the United States Immunodeficiency Network (USIDNET), a program of the Immune Deficiency Foundation. PIDs were categorized into 10 groups and their demographics, pulmonary diagnoses and procedures, infections, prophylaxis regimens, and laboratory findings were analyzed.

Noninfectious Manifestations and Complications of Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD), a primary immunodeficiency characterized by a deficient neutrophil oxidative burst and the inadequate killing of microbes, is well known to cause a significantly increased risk of invasive infection. However, infectious complications are not the sole manifestations of CGD; substantial additional morbidity is driven by noninfectious complications also. These complications can include, for example, a wide range of inflammatory diseases that affect the gastrointestinal tract, lung, skin, and genitourinary tract and overt autoimmune disease.

Analysis of T-cell repertoire diversity in Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia, eczema, and variable degrees of impaired cellular and humoral immunity. Age-dependent T-cell lymphopenia has been described in WAS, however, the diversity of the T-cell compartment over time in these patients has not been characterized. We have used complementarity-determining region 3 (CDR3) size distribution analysis to assess T-cell receptor (TCR) Vbeta repertoire in 13 patients with WAS.

Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family.

We previously reported on a 43-year-old patient with Wiskott-Aldrich syndrome (WAS) who experienced progressive clinical improvement and revertant T-cell mosaicism. Deletion of the disease-causing 6-bp insertion was hypothesized to have occurred by DNA polymerase slippage. We now describe 2 additional patients from the same family who also had revertant T lymphocytes that showed selective in vivo advantage.

Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T- and B-cell lineages.

Somatic mosaicism because of in vivo reversion has been recently reported in a small number of patients affected with Wiskott-Aldrich syndrome (WAS). Flow cytometry analysis of WAS protein (WASP) expression has shown that these patients carried revertant cells only among T lymphocytes. Here, we have used high-resolution capillary electrophoresis to analyze genomic DNA from highly purified cells of one of these patients and detected revertant sequences also within the B-cell fraction.

Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings.

Revertant mosaicism due to true back mutations or second-site mutations has been identified in several inherited disorders. The occurrence of revertants is considered rare, and the underlying genetic mechanisms remain mostly unknown. Here we describe somatic mosaicism in two brothers affected with Wiskott-Aldrich syndrome (WAS).

Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial.

The first human gene therapy experiment begun in September 1990 used a retroviral vector containing the human adenosine deaminase (ADA) cDNA to transduce mature peripheral blood lymphocytes from patients with ADA deficiency, an inherited disorder of immunity. Two patients who had been treated with intramuscular injections of pegylated bovine ADA (PEG-ADA) for 2 to 4 years were enrolled in this trial and each received a total of approximately 10(11) cells in 11 or 12 infusions over a period of about 2 years. No adverse events were observed.