Severe combined immunodeficiency—an update

Cirillo, Emilia; Giardino, Giuliana; Gallo, Vera; D’Assante, Roberta; Grasso, Fiorentino; Romanò, Roberta; Lillo, Cristina; Galasso, Giovanni; Pignata, Claudio

doi:10.1111/nyas.12849

Cited by 87 publications

(91 citation statements)

References 126 publications

(219 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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“…To date, more than 20 genetic alterations have been identified as responsible for the disease [1]. Among these, the FOXN1 gene mutation, causative of the nude SCID phenotype, is the unique condition in which the immunological defect is related to an alteration of the thymic epithelial stroma and not to an intrinsic defect of the hematopoietic cell.…”

Section: Introductionmentioning

confidence: 99%

FOXN1 Deficiency: from the Discovery to Novel Therapeutic Approaches

et al. 2017

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Since the discovery of FOXN1 deficiency, the human counterpart of the nude mouse, a growing body of evidence investigating the role of FOXN1 in thymus and skin, has been published. FOXN1 has emerged as fundamental for thymus development, function, and homeostasis, representing the master regulator of thymic epithelial and T cell development. In the skin, it also plays a pivotal role in keratinocytes and hair follicle cell differentiation, although the underlying molecular mechanisms still remain to be fully elucidated. The nude severe combined immunodeficiency phenotype is indeed characterized by the clinical hallmarks of athymia with severe T cell immunodeficiency, congenital alopecia, and nail dystrophy. In this review, we summarize recent discoveries in the field and give interesting perspective about new and promising therapeutic approaches for disorders of immune system with athymia.

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“…Primary immunodeficiencies (PIDs) are genetic disorders in which part of the immune system is missing or does not function normally . Severe combined immunodeficiency is the most severe form of PID and is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in heterogeneous clinical presentation . In addition to severe combined immunodeficiency, Wiskott‐Aldrich syndrome, hyper‐IgM syndrome, and severe congenital neutropenia were included with typical diseases that required reconstitution of the immune system.…”

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confidence: 99%