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ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a combined immunodeficiency with a broad clinical phenotype, including not only an increased propensity for sinopulmonary and herpesviruses infections but also immune dysregulation, such as benign lymphoproliferation, autoimmunity, and maligna...

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Autores principales: Sood, Amika K., Francis, Olivia, Schworer, Stephen A., Johnson, Steven M., Smith, Benjamin D., Googe, Paul B., Wu, Eveline Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235767/
https://www.ncbi.nlm.nih.gov/pubmed/37274825
http://dx.doi.org/10.3389/fped.2023.1179788
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author Sood, Amika K.
Francis, Olivia
Schworer, Stephen A.
Johnson, Steven M.
Smith, Benjamin D.
Googe, Paul B.
Wu, Eveline Y.
author_facet Sood, Amika K.
Francis, Olivia
Schworer, Stephen A.
Johnson, Steven M.
Smith, Benjamin D.
Googe, Paul B.
Wu, Eveline Y.
author_sort Sood, Amika K.
collection PubMed
description Activated phosphoinositide 3-kinase δ syndrome (APDS) is a combined immunodeficiency with a broad clinical phenotype, including not only an increased propensity for sinopulmonary and herpesviruses infections but also immune dysregulation, such as benign lymphoproliferation, autoimmunity, and malignancy. Autoimmune complications are increasingly recognized as initial presenting features of immune dysregulation in inborn errors of immunity (IEIs), including APDS, so awareness of the spectrum of autoimmune features inherit within these disorders is critical. We present here a patient vignette to highlight cutaneous antineutrophil cytoplasmic antibody (ANCA) vasculitis as an underrecognized autoimmune manifestation of APDS. The genetic defects underlying APDS result in increased PI3Kδ signaling with aberrant downstream signaling pathways and loss of B- and/or T-cell immunologic tolerance mechanisms, which promote the development of autoimmunity. An understanding of the molecular pathways and mechanisms that lead to immune dysregulation in APDS has allowed for significant advancements in the development of precision-medicine therapeutics, such as leniolisib, to reduce the morbidity and mortality for these patients. Overall, this case and review highlight the need to maintain a high index of suspicion for IEIs, such as APDS, in those presenting with autoimmunity in combination with a dysregulated immune phenotype for prompt diagnosis and targeted intervention.
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spelling pubmed-102357672023-06-03 ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome Sood, Amika K. Francis, Olivia Schworer, Stephen A. Johnson, Steven M. Smith, Benjamin D. Googe, Paul B. Wu, Eveline Y. Front Pediatr Pediatrics Activated phosphoinositide 3-kinase δ syndrome (APDS) is a combined immunodeficiency with a broad clinical phenotype, including not only an increased propensity for sinopulmonary and herpesviruses infections but also immune dysregulation, such as benign lymphoproliferation, autoimmunity, and malignancy. Autoimmune complications are increasingly recognized as initial presenting features of immune dysregulation in inborn errors of immunity (IEIs), including APDS, so awareness of the spectrum of autoimmune features inherit within these disorders is critical. We present here a patient vignette to highlight cutaneous antineutrophil cytoplasmic antibody (ANCA) vasculitis as an underrecognized autoimmune manifestation of APDS. The genetic defects underlying APDS result in increased PI3Kδ signaling with aberrant downstream signaling pathways and loss of B- and/or T-cell immunologic tolerance mechanisms, which promote the development of autoimmunity. An understanding of the molecular pathways and mechanisms that lead to immune dysregulation in APDS has allowed for significant advancements in the development of precision-medicine therapeutics, such as leniolisib, to reduce the morbidity and mortality for these patients. Overall, this case and review highlight the need to maintain a high index of suspicion for IEIs, such as APDS, in those presenting with autoimmunity in combination with a dysregulated immune phenotype for prompt diagnosis and targeted intervention. Frontiers Media S.A. 2023-05-19 /pmc/articles/PMC10235767/ /pubmed/37274825 http://dx.doi.org/10.3389/fped.2023.1179788 Text en © 2023 Sood, Francis, Schworer, Johnson, Smith, Googe and Wu. 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
Sood, Amika K.
Francis, Olivia
Schworer, Stephen A.
Johnson, Steven M.
Smith, Benjamin D.
Googe, Paul B.
Wu, Eveline Y.
ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome
title ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome
title_full ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome
title_fullStr ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome
title_full_unstemmed ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome
title_short ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome
title_sort anca vasculitis expands the spectrum of autoimmune manifestations of activated pi3 kinase δ syndrome
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235767/
https://www.ncbi.nlm.nih.gov/pubmed/37274825
http://dx.doi.org/10.3389/fped.2023.1179788
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