Severe Combined Immunodeficiency Disorders

Chinn, Iván K.; Shearer, William T.

doi:10.1016/j.iac.2015.07.002

Cited by 73 publications

(50 citation statements)

References 160 publications

(163 reference statements)

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“…Infants with classical SCID often have recurrent or persistent mucosal and/or cutaneous candidiasis involving the orodigestive tract, genital area, nails, and skin. Pneumocystis jiroveci pneumonia (PCP) and invasive fungal infections (IFIs) including systemic candidiasis and aspergillosis are often life-threatening (100, 101). Interestingly, endemic mycoses have not been described in SCID babies, at least in the English literature.…”

Section: Pids Underlying Fungal Infectionsmentioning

confidence: 99%

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Lee

Lau

2017

Front. Immunol.

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The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique climatic and geographical regions.

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Section: Pids Underlying Fungal Infectionsmentioning

confidence: 99%

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Lee

Lau

2017

Front. Immunol.

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“…SCID patients typically present in infancy with severe bacterial, viral and opportunistic infections. X‐linked SCID (X‐SCID) represents the most common cause of SCID and is a result of defects in the γ ‐chain of the interleukin (IL)‐2R that leads to T‐ and natural killer (NK)‐cell deficiency but normal B‐cell numbers …”

Section: Use Of Bcr Repertoire Sequencing In Patients With Pidmentioning

confidence: 99%

“…X-linked SCID (X-SCID) represents the most common cause of SCID and is a result of defects in the c-chain of the interleukin (IL)-2R that leads to T-and natural killer (NK)-cell deficiency but normal B-cell numbers. 48,49 Minegishi et al 50 used BCR sequencing to study BCR repertoire development and VDJ recombination in these patients. CDR3 average length and D gene usage were similar between X-SCID patients and HC.…”

Section: Combined Immunodeficienciesmentioning

confidence: 99%

B‐cell receptor repertoire sequencing in patients with primary immunodeficiency: a review

et al. 2017

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SummaryThe advent of next-generation sequencing (NGS) now allows a detailed assessment of the adaptive immune system in health and disease. In particular, high-throughput B-cell receptor (BCR) repertoire sequencing provides detailed information about the functionality and abnormalities of the B-cell system. However, it is mostly unknown how the BCR repertoire is altered in the context of primary immunodeficiencies (PID) and whether findings are consistent throughout phenotypes and genotypes. We have performed an extensive literature search of the published work on BCR repertoire sequencing in PID patients, including several forms of predominantly antibody disorders and combined immunodeficiencies. It is somewhat surprising that BCR repertoires, even from severe clinical phenotypes, often show only mild abnormalities and that diversity or immunoglobulin gene segment usage is generally preserved to some extent. Despite the great variety of wet laboratory and analytical methods that were used in the different studies, several findings are common to most investigated PIDs, such as the increased usage of gene segments that are associated with self-reactivity. These findings suggest that BCR repertoire characteristics may be used to assess the functionality of the B-cell compartment irrespective of the underlying defect. With the use of NGS approaches, there is now the opportunity to apply BCR repertoire sequencing to multiple patients and explore the PID BCR repertoire in more detail. Ultimately, using BCR repertoire sequencing in translational research could aid the management of PID patients by improving diagnosis, estimating functionality of the immune system and improving assessment of prognosis.

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“…Severe erythroderma and exfoliative dermatitis are evident in early infancy, along with elevated IgE, infections, lymphadenopathy and hepatosplenomegaly. 20 …”

Section: Clinical Presentation Of Dock8 Deficiencymentioning

confidence: 99%

Current Status of Dedicator of Cytokinesis-Associated Immunodeficiency

Dimitrova

Freeman

2017

Dermatologic Clinics

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Synopsis DOCK8 deficiency is an autosomal recessive combined immunodeficiency disease associated with elevated IgE, atopy, recurrent sinopulmonary and cutaneous viral infections, and malignancy. The DOCK8 protein is critical for cytoskeletal organization, and deficiency impairs dendritic cell transmigration, T cell survival, and NK cell cytotoxicity. Early hematopoietic stem cell transplant is gaining prominence as a definitive treatment given the potential for severe complications and mortality in this disease. Recently, DOCK2 deficiency has been identified in several patients with early-onset invasive bacterial and viral infections.

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Severe Combined Immunodeficiency Disorders

Cited by 73 publications

References 160 publications

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

B‐cell receptor repertoire sequencing in patients with primary immunodeficiency: a review

Current Status of Dedicator of Cytokinesis-Associated Immunodeficiency

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