title: Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences.
abstract: 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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Roos-Marijn
authors.initials: RM
authors.lastname: Berbers
authors.affiliation: Department of Medical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Nierkens
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.affiliation: Department of Pediatric Infectious Disease, University of Edinburgh, UK; Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: Bogaert
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: h.leavis@umcutrecht.nl.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Leavis
mesh_terms: D000818:Animals; D015551:Autoimmunity; D017074:Common Variable Immunodeficiency / Q000276:immunology / Q000382:microbiology*; D064806:Dysbiosis / Q000276:immunology* / Q000382:microbiology; D019317:Evidence-Based Medicine; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D018928:Immunity, Mucosal; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D018448:Models, Immunological
keywords: autoimmune disease; autoinflammation; common variable immunodeficiency; immune dysregulation; microbiome