scholarly journals Monogenic Adult-Onset Inborn Errors of Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Frederik Staels ◽  
Tom Collignon ◽  
Albrecht Betrains ◽  
Margaux Gerbaux ◽  
Mathijs Willemsen ◽  
...  
Keyword(s):  
Pediatric Population ◽  
Adaptive Immune System ◽  
Adult Onset ◽  
Inborn Errors ◽  
Adaptive Immune ◽  
Delayed Onset ◽  
Inborn Errors Of Immunity ◽  
Heterogenous Group ◽  
Targeted Treatments ◽  
Generation Sequencing

Inborn errors of immunity (IEI) are a heterogenous group of disorders driven by genetic defects that functionally impact the development and/or function of the innate and/or adaptive immune system. The majority of these disorders are thought to have polygenic background. However, the use of next-generation sequencing in patients with IEI has led to an increasing identification of monogenic causes, unravelling the exact pathophysiology of the disease and allowing the development of more targeted treatments. Monogenic IEI are not only seen in a pediatric population but also in adulthood, either due to the lack of awareness preventing childhood diagnosis or due to a delayed onset where (epi)genetic or environmental factors can play a role. In this review, we discuss the mechanisms accounting for adult-onset presentations and provide an overview of monogenic causes associated with adult-onset IEI.

scholarly journals Gut Microbiota–Host Interactions in Inborn Errors of Immunity

2021 ◽  
Vol 22 (3) ◽  
pp. 1416
Author(s):  
Riccardo Castagnoli ◽  
Francesca Pala ◽  
Marita Bosticardo ◽  
Amelia Licari ◽  
Ottavia M. Delmonte ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Wide Spectrum ◽  
Adaptive Immune System ◽  
Clinical Feature ◽  
Inborn Errors ◽  
Mucosal Permeability ◽  
Microbial Dysbiosis ◽  
Inborn Errors Of Immunity ◽  
Key Aspects ◽  
And Function

Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host’s innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.

Approach to genetic diagnosis of inborn errors of immunity through next-generation sequencing

2021 ◽  
Vol 137 ◽  
pp. 57-66
Author(s):  
Esmat Karimi ◽  
Fatemeh Mahmoudian ◽  
Saul O. Lugo Reyes ◽  
Umair Ahmed Bargir ◽  
Manisha Madkaikar ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Diagnosis ◽  
Next Generation ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity ◽  
Generation Sequencing

Next generation sequencing analysis of consecutive Russian patients with clinical suspicion of inborn errors of immunity

2020 ◽  
Vol 98 (3) ◽  
pp. 231-239
Author(s):  
Evgeny N. Suspitsin ◽  
Marina N. Guseva ◽  
Mikhail M. Kostik ◽  
Anna P. Sokolenko ◽  
Nataliya V. Skripchenko ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Clinical Suspicion ◽  
Sequencing Analysis ◽  
Next Generation ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity ◽  
Next Generation Sequencing Analysis ◽  
Generation Sequencing

scholarly journals Recent advances in primary immunodeficiency: from molecular diagnosis to treatment

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 194 ◽  
Author(s):  
Giorgia Bucciol ◽  
Isabelle Meyts
Keyword(s):  
Gene Therapy ◽  
Primary Immunodeficiency ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity ◽  
Technological Advances ◽  
Fast Pace ◽  
Recent Developments ◽  
Generation Sequencing ◽  
Review Current ◽  
Diagnostics And Therapy

The technological advances in diagnostics and therapy of primary immunodeficiency are progressing at a fast pace. This review examines recent developments in the field of inborn errors of immunity, from their definition to their treatment. We will summarize the challenges posed by the growth of next-generation sequencing in the clinical setting, touch briefly on the expansion of the concept of inborn errors of immunity beyond the classic immune system realm, and finally review current developments in targeted therapies, stem cell transplantation, and gene therapy.

scholarly journals Insights into the Human Virome Using CRISPR Spacers from Microbiomes

Viruses ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 479 ◽  
Author(s):  
Claudio Hidalgo-Cantabrana ◽  
Rosemary Sanozky-Dawes ◽  
Rodolphe Barrangou
Keyword(s):  
Pathogenic Bacteria ◽  
Human Microbiome ◽  
Adaptive Immune System ◽  
Metagenomic Data ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Adaptive Immune ◽  
Associated Proteins ◽  
Health And Disease ◽  
Generation Sequencing

Due to recent advances in next-generation sequencing over the past decade, our understanding of the human microbiome and its relationship to health and disease has increased dramatically. Yet, our insights into the human virome, and its interplay with important microbes that impact human health, is relatively limited. Prokaryotic and eukaryotic viruses are present throughout the human body, comprising a large and diverse population which influences several niches and impacts our health at various body sites. The presence of prokaryotic viruses like phages, has been documented at many different body sites, with the human gut being the richest ecological niche. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated proteins constitute the adaptive immune system of bacteria, which prevents attack by invasive nucleic acid. CRISPR-Cas systems function by uptake and integration of foreign genetic element sequences into the CRISPR array, which constitutes a genomic archive of iterative vaccination events. Consequently, CRISPR spacers can be investigated to reconstruct interplay between viruses and bacteria, and metagenomic sequencing data can be exploited to provide insights into host-phage interactions within a niche. Here, we show how the CRISPR spacer content of commensal and pathogenic bacteria can be used to determine the evidence of their phage exposure. This framework opens new opportunities for investigating host-virus dynamics in metagenomic data, and highlights the need to dedicate more efforts for virome sampling and sequencing.

scholarly journals Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee

2020 ◽  
Vol 40 (1) ◽  
pp. 24-64 ◽  
Author(s):  
Stuart G. Tangye ◽  
Waleed Al-Herz ◽  
Aziz Bousfiha ◽  
Talal Chatila ◽  
Charlotte Cunningham-Rundles ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rapid Identification ◽  
Expert Committee ◽  
International Union ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity ◽  
Immunological Mechanisms ◽  
Gene Defects ◽  
Generation Sequencing

Abstract We report the updated classification of Inborn Errors of Immunity/Primary Immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies. The application of next-generation sequencing continues to expedite the rapid identification of novel gene defects, rare or common; broaden the immunological and clinical phenotypes of conditions arising from known gene defects and even known variants; and implement gene-specific therapies. These advances are contributing to greater understanding of the molecular, cellular, and immunological mechanisms of disease, thereby enhancing immunological knowledge while improving the management of patients and their families. This report serves as a valuable resource for the molecular diagnosis of individuals with heritable immunological disorders and also for the scientific dissection of cellular and molecular mechanisms underlying inborn errors of immunity and related human diseases.

scholarly journals Functional genetics in inborn errors of immunity

2021 ◽  
pp. FRD11
Author(s):  
Emma Rey-Jurado ◽  
María Cecilia Poli
Keyword(s):  
Primary Immunodeficiencies ◽  
Genetic Defects ◽  
Potential Candidate ◽  
Functional Validation ◽  
Inborn Errors ◽  
Susceptibility To Infection ◽  
Inborn Errors Of Immunity ◽  
Genes Encoding ◽  
Generation Sequencing ◽  
Increased Susceptibility

Inborn errors of immunity are genetic defects of the immune system, causing increased susceptibility to infection, autoinflammation, autoimmunity and immune dysregulation. Next-generation sequencing has enabled exponential identification of novel inborn errors of immunity due to mutations in genes encoding for proteins that participate in the immune response. However, genomic sequencing often yields multiple variants in potential candidate genes, hence functional validation of these genetic defects becomes paramount to achieve diagnosis and discovery. Genome-editing technologies such as CRISPR-Cas9 have allowed exponential advances on discovery of new primary immunodeficiencies, enabling appropriate diagnosis and treatment. This review summarizes the heterogeneous clinical presentation of primary immunodeficiencies and contextualizes the rationale for functional validation studies to achieve diagnosis and discovery, subsequently leading to the application of directed therapies.

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