PRIMARY IMMUNE DEFICIENCY DISEASE: Edited by Bruce D. Mazer and Stephen JollesThe autoimmune conundrum in common variable immunodeficiency disordersvan de Ven, Annick A.J.M.; Warnatz, Klaus Author Information aDivision of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, the Netherlands bCenter for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, Freiburg, Germany Correspondence to Klaus Warnatz, MD, Center for Chronic Immunodeficiency, University Medical Center and University of Freiburg, Breisacherstr.117, Freiburg Germany. Tel: +49 76127077640; fax: +49 76127077600; e-mail: [email protected] Current Opinion in Allergy and Clinical Immunology: December 2015 - Volume 15 - Issue 6 - p 514-524 doi: 10.1097/ACI.0000000000000218 Buy Metrics Abstract Purpose of review Autoimmune and inflammatory manifestations are the biggest clinical challenge in the care of patients with common variable immunodeficiency (CVID). The increasing pathogenic knowledge and potential therapeutic implications require a new evaluation of the status quo. Box 1: no caption availableRecent findings The conundrum of the simultaneous manifestation of primary immunodeficiency and autoimmune disease (AID) is increasingly elucidated by newly discovered genetic defects. Thus, cytotoxic T lymphocyte-associated antigen 4 or caspase-9 deficiency presenting with CVID-like phenotypes reiterate concepts of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome and autoimmune lymphoproliferative syndrome. Activating signaling defects downstream of antigen or cytokine receptors are often associated with loss-of-tolerance in the affected patients. Increasingly, forms of combined immunodeficiency are discovered among CVID-like patients. Although different autoimmune manifestations often coincide in the same patient their immunopathology varies. Treatment of AID in CVID remains a challenge, but based on a better definition of the immunopathology first attempts of targeted treatment have been made. Summary The increasing comprehension of immunological concepts promoting AID in CVID will allow better and in some cases possibly even targeted treatment. A genetic diagnosis therefore becomes important information in this group of patients, especially in light of the fact that some patients might require hematopoietic stem cell transplantation because of their underlying immunodeficiency. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.