Journal of Clinical Immunology

, Volume 39, Issue 1, pp 30–36 | Cite as

Autoimmunity and Inflammation in CVID: a Possible Crosstalk between Immune Activation, Gut Microbiota, and Epigenetic Modifications

  • Silje F. JørgensenEmail author
  • Børre Fevang
  • Pål Aukrust
Original Article


Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency among adults and is characterized by a B cell dysfunction and increased risk of respiratory tract infections with encapsulated bacteria. However, a large proportion of patients also has inflammatory and autoimmune complications. It may seem like a paradox that immunodeficiency and inflammation/autoimmunity coexist within the same individuals. In this commentary, we propose that CVID immunopathogenesis involves an interplay of genes, environmental factors, and dysregulation of immune cells, where gut microbiota and gastrointestinal inflammation can both be important contributors or endpoints to the systemic immune activation seen in CVID, and where epigenetic mechanism may be the undiscovered link between these contributors. In our opinion, these pathways could represent novel targets for therapy in CVID directed against autoimmune and inflammatory manifestations that represent the most severe complications in these patients. Considering the heterogeneous nature of CVID, these mechanisms may not be present in all patients, and different complications may be triggered by different risk factors. CVID is really a variable disease and in the future there is clearly a need for a more personalized medicine based on both genotypic and phenotypic findings.


Common variable immunodeficiency autoimmunity inflammation mucosal immunology gut microbiota epigenetic Primary immunodeficinecy 



We thank the Norwegian PSC center for the collaboration and their important research efforts upon which some of the new insights of this review article is based, particularly Johannes R. Hov and Tom H. Karlsen. We are also grateful to Tom. H. Karlsen for the inspiration to  Fig. 1. We would like to thank Kari Toverud for professional support in developing Fig. 2 of this review article.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and TransplantationOslo University HospitalOsloNorway
  2. 2.Section of Clinical Immunology and Infectious Diseases, Department of Rheumatology, Dermatology and Infectious DiseasesOslo University HospitalOsloNorway

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