Deficient T Cell Receptor Excision Circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: Implications for pathogenesis and potential detection by newborn screening

Dasouki, Majed; Okonkwo, Kingsley C.; Ray, Abhishek; Folmsbeel, Caspian K.; Gozales, Diana; Keleş, Sevgi; Puck, Jennifer M.; Chatila, Talal A.

doi:10.1016/j.clim.2011.06.003

Cited by 56 publications

(48 citation statements)

References 22 publications

(38 reference statements)

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“…11 Furthermore, the presence of congenital abnormalities and complications because of prematurity have been shown to increase the number of abnormal test results from excision circle assays, as will the detection of additional combined immunodeficiencies such as DOCK8 deficiency. 12,13 This observation is likely to be expanded to isolated abnormal KREC copy numbers, as presented here for the included samples from NBS patients. The clinical significance of low KREC levels therefore deserves further investigation and will be the subject of 2 large-scale prospective studies in Sweden and Germany.…”

Section: Diagnostic Procedures For Routine Prospective Guthrie Card Amentioning

confidence: 99%

Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR

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Fasth

et al. 2012

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Section: Diagnostic Procedures For Routine Prospective Guthrie Card Amentioning

confidence: 99%

Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR

Borte

Döbeln

Fasth

et al. 2012

Blood

179

173

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“…If neonatal screening becomes available to every neonate, then definitive treatment can be initiated immediately, which would result in up to 94% survival [43]. In addition, NBS would reveal other conditions associated with T-cell deficiency and the true incidence of SCID [50,53,54].…”

Section: Discussionmentioning

confidence: 99%

“…This report suggests that autosomal recessive hyper-IgE syndrome may be detected by TREC NBS, and this diagnosis should be considered in the evaluation of newborns with abnormal TRECs who do not have typical SCID [53].…”

Section: Severe Combined Immunodeficiencymentioning

confidence: 94%

Should Newborns be Screened for Immunodeficiency? Lessons Learned from Infants with Recurrent Otitis Media

Yilmaz-Demirdag

2011

Curr Allergy Asthma Rep

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Recurrent otitis media in children is considered one of the warning signs of primary immunodeficiencies (PIDs), particularly antibody deficiencies. Infants who have the most serious and potentially lethal form of PID, severe combined immunodeficiency (SCID), sometimes present with recurrent otitis media. Most of the time, because of the severity of the immune defect, they develop more serious and systemic infections. SCID is distinct among the PIDs and considered a pediatric emergency. Diagnosing SCID during the newborn period is crucial because survival completely depends on early diagnosis and treatment. Mortality declines significantly if immune reconstitution is established before 3.5 months of age, particularly before severe infections have occurred. However, most patients are diagnosed after they have suffered chronic or recurrent infections and developed permanent sequelae. Without institution of population-based newborn screening, most infants will miss the opportunity to live a healthy life.

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“…immunological abnormalities include reduced T cell numbers (with normal CD4/CD8 ratio) and variably decreased or normal B-and NK-cell numbers [64]. T lymphopenia may stem from a combination of poor cell expansion after antigen stimulation and decreased thymic output as evidenced by decreased T cell receptor excision circles (TRECs) found in some patients [65]. In the absence of DOCK8, failure of dendritic cell (DC) migration to lymph nodes and impaired CD4 T cell priming has been observed [66].…”

Section: Genetic Origin and Pathogenesis Of Didsmentioning

confidence: 99%

Primary Immunodeficiencies with Elevated IgE

Mogensen¹

2015

International Reviews of Immunology

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In recent years a number of primary immunodeficiencies (PIDs) characterized by elevated Immunoglobulin E (IgE) levels have been uncovered and termed as Hyper-IgE syndrome (HIES). In addition to the elevated levels of IgE, patients with these PIDs display a spectrum of infections by staphylococci and fungi, and in some cases viruses, particularly affecting skin and lungs. Most of these PIDs also have a non-infectious phenotype, comprising musculoskeletal, vascular, and neurological abnormalities. The genetic basis for the majority of conditions with elevated IgE has now been established and includes mutations in STAT3, DOCK8, TYK2, and most recently PGM3 molecules. However, in some patients with the relevant phenotype, mutations in these molecules are not identified, suggesting additional genetic etiologies of HIES not yet discovered. As the immunological and molecular basis of HIES is being unraveled, important insights are emerging that may have implications for our understanding of basic principles of immunology and protective immunity as well as for the pathogenesis and clinical management of patients with these complex and challenging PIDs. In this review, are presented the current knowledge on the clinical presentation, infectious phenotype, and the genetic and immunological pathogenesis of hyper-IgE syndromes as well as some other PIDs with elevated levels of IgE.

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Deficient T Cell Receptor Excision Circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: Implications for pathogenesis and potential detection by newborn screening

Cited by 56 publications

References 22 publications

Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR

Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR

Should Newborns be Screened for Immunodeficiency? Lessons Learned from Infants with Recurrent Otitis Media

Primary Immunodeficiencies with Elevated IgE

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