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Granulomatous inflammation in inborn errors of immunity

Granulomas have been defined as inflammatory infiltrates formed by recruitment of macrophages and T cells. The three-dimensional spherical structure typically consists of a central core of tissue resident macrophages which may merge into multinucleated giant cells surrounded by T cells at the periph...

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Autores principales: Sacco, Keith A., Gazzin, Andrea, Notarangelo, Luigi D., Delmonte, Ottavia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986611/
https://www.ncbi.nlm.nih.gov/pubmed/36891233
http://dx.doi.org/10.3389/fped.2023.1110115
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author Sacco, Keith A.
Gazzin, Andrea
Notarangelo, Luigi D.
Delmonte, Ottavia M.
author_facet Sacco, Keith A.
Gazzin, Andrea
Notarangelo, Luigi D.
Delmonte, Ottavia M.
author_sort Sacco, Keith A.
collection PubMed
description Granulomas have been defined as inflammatory infiltrates formed by recruitment of macrophages and T cells. The three-dimensional spherical structure typically consists of a central core of tissue resident macrophages which may merge into multinucleated giant cells surrounded by T cells at the periphery. Granulomas may be triggered by infectious and non-infectious antigens. Cutaneous and visceral granulomas are common in inborn errors of immunity (IEI), particularly among patients with chronic granulomatous disease (CGD), combined immunodeficiency (CID), and common variable immunodeficiency (CVID). The estimated prevalence of granulomas in IEI ranges from 1%–4%. Infectious agents causing granulomas such Mycobacteria and Coccidioides presenting atypically may be ‘sentinel’ presentations for possible underlying immunodeficiency. Deep sequencing of granulomas in IEI has revealed non-classical antigens such as wild-type and RA27/3 vaccine-strain Rubella virus. Granulomas in IEI are associated with significant morbidity and mortality. The heterogeneity of granuloma presentation in IEI presents challenges for mechanistic approaches to treatment. In this review, we discuss the main infectious triggers for granulomas in IEI and the major forms of IEI presenting with ‘idiopathic’ non-infectious granulomas. We also discuss models to study granulomatous inflammation and the impact of deep-sequencing technology while searching for infectious triggers of granulomatous inflammation. We summarize the overarching goals of management and highlight the therapeutic options reported for specific granuloma presentations in IEI.
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spelling pubmed-99866112023-03-07 Granulomatous inflammation in inborn errors of immunity Sacco, Keith A. Gazzin, Andrea Notarangelo, Luigi D. Delmonte, Ottavia M. Front Pediatr Pediatrics Granulomas have been defined as inflammatory infiltrates formed by recruitment of macrophages and T cells. The three-dimensional spherical structure typically consists of a central core of tissue resident macrophages which may merge into multinucleated giant cells surrounded by T cells at the periphery. Granulomas may be triggered by infectious and non-infectious antigens. Cutaneous and visceral granulomas are common in inborn errors of immunity (IEI), particularly among patients with chronic granulomatous disease (CGD), combined immunodeficiency (CID), and common variable immunodeficiency (CVID). The estimated prevalence of granulomas in IEI ranges from 1%–4%. Infectious agents causing granulomas such Mycobacteria and Coccidioides presenting atypically may be ‘sentinel’ presentations for possible underlying immunodeficiency. Deep sequencing of granulomas in IEI has revealed non-classical antigens such as wild-type and RA27/3 vaccine-strain Rubella virus. Granulomas in IEI are associated with significant morbidity and mortality. The heterogeneity of granuloma presentation in IEI presents challenges for mechanistic approaches to treatment. In this review, we discuss the main infectious triggers for granulomas in IEI and the major forms of IEI presenting with ‘idiopathic’ non-infectious granulomas. We also discuss models to study granulomatous inflammation and the impact of deep-sequencing technology while searching for infectious triggers of granulomatous inflammation. We summarize the overarching goals of management and highlight the therapeutic options reported for specific granuloma presentations in IEI. Frontiers Media S.A. 2023-02-20 /pmc/articles/PMC9986611/ /pubmed/36891233 http://dx.doi.org/10.3389/fped.2023.1110115 Text en © 2023 Sacco, Gazzin, Notarangelo and Delmonte. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Sacco, Keith A.
Gazzin, Andrea
Notarangelo, Luigi D.
Delmonte, Ottavia M.
Granulomatous inflammation in inborn errors of immunity
title Granulomatous inflammation in inborn errors of immunity
title_full Granulomatous inflammation in inborn errors of immunity
title_fullStr Granulomatous inflammation in inborn errors of immunity
title_full_unstemmed Granulomatous inflammation in inborn errors of immunity
title_short Granulomatous inflammation in inborn errors of immunity
title_sort granulomatous inflammation in inborn errors of immunity
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986611/
https://www.ncbi.nlm.nih.gov/pubmed/36891233
http://dx.doi.org/10.3389/fped.2023.1110115
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