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Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency
Common variable immunodeficiency (CVID) is characterized by profound primary antibody defects and frequent infections, yet autoimmune/inflammatory complications of unclear origin occur in 50% of individuals and lead to increased mortality. Here, we show that circulating bacterial 16S rDNA belonging...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525635/ https://www.ncbi.nlm.nih.gov/pubmed/34622805 http://dx.doi.org/10.1172/jci.insight.144777 |
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author | Ho, Hsi-en Radigan, Lin Bongers, Gerold El-Shamy, Ahmed Cunningham-Rundles, Charlotte |
author_facet | Ho, Hsi-en Radigan, Lin Bongers, Gerold El-Shamy, Ahmed Cunningham-Rundles, Charlotte |
author_sort | Ho, Hsi-en |
collection | PubMed |
description | Common variable immunodeficiency (CVID) is characterized by profound primary antibody defects and frequent infections, yet autoimmune/inflammatory complications of unclear origin occur in 50% of individuals and lead to increased mortality. Here, we show that circulating bacterial 16S rDNA belonging to gut commensals was significantly increased in CVID serum (P < 0.0001), especially in patients with inflammatory manifestations (P = 0.0007). Levels of serum bacterial DNA were associated with parameters of systemic immune activation, increased serum IFN-γ, and the lowest numbers of isotype-switched memory B cells. Bacterial DNA was bioactive in vitro and induced robust host IFN-γ responses, especially among patients with CVID with inflammatory manifestations. Patients with X-linked agammaglobulinemia (Bruton tyrosine kinase [BTK] deficiency) also had increased circulating bacterial 16S rDNA but did not exhibit prominent immune activation, suggesting that BTK may be a host modifier, dampening immune responses to microbial translocation. These data reveal a mechanism for chronic immune activation in CVID and potential therapeutic strategies to modify the clinical outcomes of this disease. |
format | Online Article Text |
id | pubmed-8525635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-85256352021-10-26 Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency Ho, Hsi-en Radigan, Lin Bongers, Gerold El-Shamy, Ahmed Cunningham-Rundles, Charlotte JCI Insight Research Article Common variable immunodeficiency (CVID) is characterized by profound primary antibody defects and frequent infections, yet autoimmune/inflammatory complications of unclear origin occur in 50% of individuals and lead to increased mortality. Here, we show that circulating bacterial 16S rDNA belonging to gut commensals was significantly increased in CVID serum (P < 0.0001), especially in patients with inflammatory manifestations (P = 0.0007). Levels of serum bacterial DNA were associated with parameters of systemic immune activation, increased serum IFN-γ, and the lowest numbers of isotype-switched memory B cells. Bacterial DNA was bioactive in vitro and induced robust host IFN-γ responses, especially among patients with CVID with inflammatory manifestations. Patients with X-linked agammaglobulinemia (Bruton tyrosine kinase [BTK] deficiency) also had increased circulating bacterial 16S rDNA but did not exhibit prominent immune activation, suggesting that BTK may be a host modifier, dampening immune responses to microbial translocation. These data reveal a mechanism for chronic immune activation in CVID and potential therapeutic strategies to modify the clinical outcomes of this disease. American Society for Clinical Investigation 2021-10-08 /pmc/articles/PMC8525635/ /pubmed/34622805 http://dx.doi.org/10.1172/jci.insight.144777 Text en © 2021 Ho et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Ho, Hsi-en Radigan, Lin Bongers, Gerold El-Shamy, Ahmed Cunningham-Rundles, Charlotte Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency |
title | Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency |
title_full | Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency |
title_fullStr | Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency |
title_full_unstemmed | Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency |
title_short | Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency |
title_sort | circulating bioactive bacterial dna is associated with immune activation and complications in common variable immunodeficiency |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525635/ https://www.ncbi.nlm.nih.gov/pubmed/34622805 http://dx.doi.org/10.1172/jci.insight.144777 |
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