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

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Abstract

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.

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Fig. 1: The spectrum of contribution by environmental factors and genetics in immunodeficiency conditions and the possible role of epigenetics.
Fig. 2: Integrated overview of suggested immunopathogenic mechanisms in common variable immunodeficiency (CVID).

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Acknowledgements

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.

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Authors and Affiliations

  1. Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Nydalen, P.O. Box 4950, 0424, Oslo, Norway

    Silje F. Jørgensen, Børre Fevang & Pål Aukrust

  2. Section of Clinical Immunology and Infectious Diseases, Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    Silje F. Jørgensen, Børre Fevang & Pål Aukrust

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  1. Silje F. Jørgensen
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Correspondence to Silje F. Jørgensen.

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Jørgensen, S.F., Fevang, B. & Aukrust, P. Autoimmunity and Inflammation in CVID: a Possible Crosstalk between Immune Activation, Gut Microbiota, and Epigenetic Modifications. J Clin Immunol 39, 30–36 (2019). https://doi.org/10.1007/s10875-018-0574-z

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  • DOI: https://doi.org/10.1007/s10875-018-0574-z

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