Severe Combined Immunodeficiences: New and Old Scenarios

Aloj, Giuseppina; Giardino, Giuliana; Valentino, Leopoldo; Maio, Filomena; Gallo, Vera; Esposito, Tiziana; Naddei, Roberta; Cirillo, Emilia; Pignata, Claudio

doi:10.3109/08830185.2011.644607

Cited by 44 publications

(31 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The patients were selected on the basis of clinical features and abnormal immune parameters (20). The clinical criteria included one or more of the following features: opportunistic infections, granuloma, chronic mucocutaneous candidiasis (CMC), intractable diarrhea, bronchiectasis, and severe autoimmunity.…”

Section: Methodsmentioning

confidence: 99%

Diagnostics of Primary Immunodeficiencies through Next-Generation Sequencing

et al. 2016

Self Cite

View full text Add to dashboard Cite

BackgroundRecently, a growing number of novel genetic defects underlying primary immunodeficiencies (PIDs) have been identified, increasing the number of PID up to more than 250 well-defined forms. Next-generation sequencing (NGS) technologies and proper filtering strategies greatly contributed to this rapid evolution, providing the possibility to rapidly and simultaneously analyze large numbers of genes or the whole exome.ObjectiveTo evaluate the role of targeted NGS and whole exome sequencing (WES) in the diagnosis of a case series, characterized by complex or atypical clinical features suggesting a PID, difficult to diagnose using the current diagnostic procedures.MethodsWe retrospectively analyzed genetic variants identified through targeted NGS or WES in 45 patients with complex PID of unknown etiology.ResultsForty-seven variants were identified using targeted NGS, while 5 were identified using WES. Newly identified genetic variants were classified into four groups: (I) variations associated with a well-defined PID, (II) variations associated with atypical features of a well-defined PID, (III) functionally relevant variations potentially involved in the immunological features, and (IV) non-diagnostic genotype, in whom the link with phenotype is missing. We reached a conclusive genetic diagnosis in 7/45 patients (~16%). Among them, four patients presented with a typical well-defined PID. In the remaining three cases, mutations were associated with unexpected clinical features, expanding the phenotypic spectrum of typical PIDs. In addition, we identified 31 variants in 10 patients with complex phenotype, individually not causative per se of the disorder.ConclusionNGS technologies represent a cost-effective and rapid first-line genetic approach for the evaluation of complex PIDs. WES, despite a moderate higher cost compared to targeted, is emerging as a valuable tool to reach in a timely manner, a PID diagnosis with a considerable potential to draw genotype–phenotype correlation. Nevertheless, a large fraction of patients still remains without a conclusive diagnosis. In these patients, the sum of non-diagnostic variants might be proven informative in future studies with larger cohorts of patients.

show abstract

Section: Methodsmentioning

confidence: 99%

Diagnostics of Primary Immunodeficiencies through Next-Generation Sequencing

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, several novel syndromes with unusual phenotypes have been described [1,2]. However, in a number of patients suffering from severe and sometimes life-threatening infections, in which an immunological disorder is suspected, the underlying genetic defect responsible for the immunodeficiency still remains to be elucidated [3]. Recently, a higher susceptibility to intracellular pathogens and, in particular, atypical mycobacterial and salmonella infections has been described in patients with genetic alterations of the IL-12 receptor (IL-12R) [4-9].…”

Section: Introductionmentioning

confidence: 99%

Interleukin 12 receptor deficiency in a child with recurrent bronchopneumonia and very high IgE levels

et al. 2012

Self Cite

View full text Add to dashboard Cite

Interleukin-12 (IL-12) is involved in cellular immune responses against intracellular pathogens by promoting the generation of T naive in T helper 1 (Th1) cells and by increasing interferon-gamma (IFN-gamma) production from T and natural killer (NK) cells. A defective induction of a Th1 response may lead to a higher risk of infections, and, in particular, infections due to typical and atypical Mycobacteria. We report on the case of a girl with suffering from recurrent bronchopneumonia associated with very high serum IgE levels, who exhibited a profound impairment of the Th1 generation associated with a novel mutation in the exon 5 of the IL-12R β1 gene (R156H). Our data suggest that in children with severe and recurrent infections, even in the absence of a mycobacterial infection, functional and/or genetic alterations of the molecular mechanisms governing Th1/Th2 homeostasis might be responsible for an atypical immunodeficiency and, therefore, should be investigated in these patients.

show abstract

“…There are a number of genetic mutations leading to SCID, including mutations in IL2RG , JAK3 , IL7RA , RAG1 and RAG2 , DCLRE1C and ADA among others [68–70]. The incidence of SCID is estimated to be around 1/50,000 live births, with a higher prevalence in males, as the most commonly identified mutation (IL2RG) is inherited in an X-linked fashion [71]. …”

Section: Immunoglobulin Therapy In Immune Deficienciesmentioning

confidence: 99%

An Update on the Use of Immunoglobulin for the Treatment of Immunodeficiency Disorders

Albin

Cunningham‐Rundles

2014

Immunotherapy

View full text Add to dashboard Cite

For patients with significant antibody deficiencies, immunoglobulin therapy is the mainstay of treatment as it significantly reduces both the frequency and severity of infections. The formulations and delivery methods of immunoglobulin have evolved over time, and continued improvements have allowed for increased access to this effective medication. This review is an update on the current status of immunoglobulin therapy in immunodeficiency disorders, and discusses the mechanisms, forms and dosing, and indications for immunoglobulin replacement.

show abstract

Severe Combined Immunodeficiences: New and Old Scenarios

Cited by 44 publications

References 162 publications

Diagnostics of Primary Immunodeficiencies through Next-Generation Sequencing

Diagnostics of Primary Immunodeficiencies through Next-Generation Sequencing

Interleukin 12 receptor deficiency in a child with recurrent bronchopneumonia and very high IgE levels

An Update on the Use of Immunoglobulin for the Treatment of Immunodeficiency Disorders

Contact Info

Product

Resources

About