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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1179788/full |
| _version_ | 1797823619753050112 |
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| author | Amika K. Sood Olivia Francis Stephen A. Schworer Stephen A. Schworer Steven M. Johnson Benjamin D. Smith Paul B. Googe Eveline Y. Wu Eveline Y. Wu |
| author_facet | Amika K. Sood Olivia Francis Stephen A. Schworer Stephen A. Schworer Steven M. Johnson Benjamin D. Smith Paul B. Googe Eveline Y. Wu Eveline Y. Wu |
| author_sort | Amika K. Sood |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-13T10:26:35Z |
| format | Article |
| id | doaj.art-2ba2c8a666004f18bcd4953da2fd21c4 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-03-13T10:26:35Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-2ba2c8a666004f18bcd4953da2fd21c42023-05-19T06:37:09ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-05-011110.3389/fped.2023.11797881179788ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndromeAmika K. Sood0Olivia Francis1Stephen A. Schworer2Stephen A. Schworer3Steven M. Johnson4Benjamin D. Smith5Paul B. Googe6Eveline Y. Wu7Eveline Y. Wu8Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, The University of North Carolina, Chapel Hill, NC, United StatesDivision of Allergy/Immunology, Department of Pediatrics, The University of North Carolina, Chapel Hill, NC, United StatesDivision of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, The University of North Carolina, Chapel Hill, NC, United StatesDivision of Allergy/Immunology, Department of Pediatrics, The University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, United StatesDivision of Pediatric Radiology, Department of Radiology, The University of North Carolina, Chapel Hill, NC, United StatesDermatopathology, Department of Dermatology, The University of North Carolina, Chapel Hill, NC, United StatesDivision of Allergy/Immunology, Department of Pediatrics, The University of North Carolina, Chapel Hill, NC, United StatesDivision of Rheumatology, Department of Pediatrics, The University of North Carolina, Chapel Hill, NC, United StatesActivated 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.https://www.frontiersin.org/articles/10.3389/fped.2023.1179788/fullactivated PI3 kinase delta syndromeautoimmuneANCA vasculitisimmunodeficiencyinborn errors of immunityimmune dysregulation |
| spellingShingle | Amika K. Sood Olivia Francis Stephen A. Schworer Stephen A. Schworer Steven M. Johnson Benjamin D. Smith Paul B. Googe Eveline Y. Wu Eveline Y. Wu ANCA vasculitis expands the spectrum of autoimmune manifestations of activated PI3 kinase δ syndrome Frontiers in Pediatrics activated PI3 kinase delta syndrome autoimmune ANCA vasculitis immunodeficiency inborn errors of immunity immune dysregulation |
| 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 | activated PI3 kinase delta syndrome autoimmune ANCA vasculitis immunodeficiency inborn errors of immunity immune dysregulation |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1179788/full |
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