Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences
Roos-Marijn Berbers, Stefan Nierkens, Jacob M. van Laar, Debby Bogaert, Helen L. Leavis
Publication stage: In Press Corrected Proof
Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic immune dysregulation. Here, we critically review the current evidence for a role of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible immunologic mechanisms behind causes and consequences of microbial dysbiosis in CVID. We integrate this evidence into a model describing a role for the gut microbiota in the maintenance of inflammation and immune dysregulation in CVID, and suggest research strategies to contribute to the development of new diagnostic tools and therapeutic targets.
The etiology of CVID and associated immune dysregulation remains incompletely understood but several lines of evidence now suggest a role for increased levels of microbial translocation.
Microbial translocation in CVID is linked to systemic inflammation and cell exhaustion, and this process may persist even under immunoglobulin substitution therapy.
Systemic inflammation and cell exhaustion are associated with immune dysregulation symptoms in CVID, such as autoimmunity, lymphoproliferation, malignancy, and granulomatous disease.
CVID patients with immune dysregulation have reduced microbial diversity in their gut compared to CVID patients without immune dysregulation and healthy controls.
microbiome, common variable immunodeficiency, immune dysregulation, autoimmune disease, autoinflammation
Topics with scientific, medical or general health related information and discussion that is not specifically related to Lyme disease.
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http://www.cell.com/trends/immunology/a ... 16)30204-6