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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-10-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.144777 |
| _version_ | 1818549323432984576 |
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| author | Hsi-en Ho Lin Radigan Gerold Bongers Ahmed El-Shamy Charlotte Cunningham-Rundles |
| author_facet | Hsi-en Ho Lin Radigan Gerold Bongers Ahmed El-Shamy Charlotte Cunningham-Rundles |
| author_sort | Hsi-en Ho |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T08:31:52Z |
| format | Article |
| id | doaj.art-da397dc368844e5ca5dfbc7cd3c4f4b8 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T08:31:52Z |
| publishDate | 2021-10-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-da397dc368844e5ca5dfbc7cd3c4f4b82022-12-22T00:31:05ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-10-01619Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiencyHsi-en HoLin RadiganGerold BongersAhmed El-ShamyCharlotte Cunningham-RundlesCommon 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.https://doi.org/10.1172/jci.insight.144777ImmunologyInflammation |
| spellingShingle | Hsi-en Ho Lin Radigan Gerold Bongers Ahmed El-Shamy Charlotte Cunningham-Rundles Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency JCI Insight Immunology Inflammation |
| 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 | Immunology Inflammation |
| url | https://doi.org/10.1172/jci.insight.144777 |
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