Clinical Phenotypes of Hyper-IgM Syndromes

Morena, M. Teresa de la

doi:10.1016/j.jaip.2016.09.013

Cited by 81 publications

(49 citation statements)

References 96 publications

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“…Patients are susceptible to opportunistic infections including PCP, cryptosporidiosis, and mycobacterial infections due to impaired interaction between T-cells and antigen-presenting cells (APCs). In addition, the failure of B-cell immunoglobulin (Ig) isotype switching results in markedly low serum IgG and IgA, while IgM is elevated (108, 109). Disseminated and cutaneous forms of histoplasmosis have been reported in eight patients in patients with X-linked hyper-IgM disorder (Table 4).…”

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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“…Clinical phenotype, pathogenesis, and prognosis related to the treatment of this specific form are well characterized. Elevated IgM levels were also reported in other well-defined immunodeficiencies, such as nuclear factor κB (NF-κB) essential modulator (NEMO), recombination-activating gene (RAG) 2, lipopolysaccharide-responsive beige-like anchor (LRBA), ataxia telangiectasia mutated (ATM), ARTEMIS, and dedicator of cytokinesis (DOCK) 2 deficiency [3,[18][19][20][21][22][23]. Most of these conditions are characterized by increased susceptibility to malignancies and infections.…”

Section: Introductionmentioning

confidence: 91%

“…High IgM levels are found in rare immunological disorders, such as hyper IgM (HIGM) syndromes, but also in autoimmune or acquired infectious diseases [1][2][3]. Elevated monoclonal IgM levels are also found in B-cell lymphoproliferative disorders (LPD) [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…HIGM type 2 (OMIM # 605258) which is due to mutations in AID gene, type 3 (OMIM # 606843) which is caused by CD40 defects, and type 5 (OMIM # 608106) which is caused by mutations in the uracil DNA glycosylase (UNG) are inherited in an autosomal recessive manner. HIGM type 4 (OMIM # 608184) is a condition with an undefined genetic cause, phenotypically similar to type 2 [3]. An autosomal-dominant form due to mutations in the C-terminal region of AID has been described in a few patients [11].…”

Section: Introductionmentioning

confidence: 99%

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Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels

Gallo

Cirillo

Prencipe

et al. 2020

JCM

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Very high IgM levels represent the hallmark of hyper IgM (HIGM) syndromes, a group of primary immunodeficiencies (PIDs) characterized by susceptibility to infections and malignancies. Other PIDs not fulfilling the diagnostic criteria for HIGM syndromes can also be characterized by high IgM levels and susceptibility to malignancies. The aim of this study is to characterize clinical phenotype, immune impairment, and pathogenic mechanism in six patients with very high IgM levels in whom classical HIGM syndromes were ruled out. The immunological analysis included extended B-cell immunophenotyping, evaluation of class switch recombination and somatic hypermutation, and next generation sequencing (NGS). Recurrent or severe infections and chronic lung changes at the diagnosis were reported in five out of six and two out of six patients, respectively. Five out of six patients showed signs of lymphoproliferation and four patients developed malignancies. Four patients showed impaired B-cell homeostasis. Class switch recombination was functional in vivo in all patients. NGS revealed, in one case, a pathogenic mutation in PIK3R1. In a second case, the ITPKB gene, implicated in B-and T-cell development, survival, and activity was identified as a potential candidate gene. Independent of the genetic basis, very high IgM levels represent a risk factor for the development of recurrent infections leading to chronic lung changes, lymphoproliferation, and high risk of malignancies.

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“…The articles found here start with reviews of 2 of the more prevalent medical complications of primary immune deficiency: autoimmunity by Walter et al 1 and lung disease by Schussler et al 2 In both articles, the central themes concern how immune dysregulation, a common aspect of immune deficiency, leads to additional organ dysfunction, the mechanisms that underlie these events, and how understanding these processes has led to improved treatment and more targeted therapies. In a third clinical management review, de la Morena 3 describe her recent compilation of data describing the overall phenotypes found in a large cohort of subjects with the hyper-IgM syndrome, concentrating on the X-linked version of this immune defect. Few large series describing the clinical course of this rare immune deficiency have appeared, making this a valuable and timely update.…”

mentioning

confidence: 99%

Primary Immunodeficiency: New Insights and Practical Clinical Approaches

Cunningham‐Rundles

2016

The Journal of Allergy and Clinical Immunology: In Practice

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Clinical Phenotypes of Hyper-IgM Syndromes

Cited by 81 publications

References 96 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

Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels

Primary Immunodeficiency: New Insights and Practical Clinical Approaches

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