title: Common variable immunodeficiency and autoimmunity--an inconvenient truth.
abstract: Coexisting morbidities in CVID include bronchiectasis, autoimmunity and malignancies. The incidence of autoimmune disease in CVID patients may approach 20% of cases. The most common autoimmune disease found in CVID patients is autoimmune cytopenia, but rheumatoid arthritis, lupus, and now primary biliary cirrhosis have also been reported. The coexistence of immunodeficiency and autoimmunity appears paradoxical, since one represents a hypoimmune state and the other a hyperimmune state. However, this paradox may not actually be all that implausible due to the complex nature of immune cells, signaling pathways and their interactions. The cellular alterations in combined variable immunodeficiency include a range of T and B cell abnormalities. Selective immune derangements found in CVID include a downregulation of regulatory T cells (Treg cells), accelerated T cell apoptosis, abnormal cytokine production secondary to cytokine gene polymorphisms and increased autoreactive B cell production. The impact of these abnormalities on T and B cell interaction may not only explain the immunodeficiency but also the development of autoimmunity in select groups of patients with CVID. The variability in the clinical manifestations of CVID as a result of this immune interaction suggests that CVID is not one disease but many. This is important because it follows that the treatment of CVID may not always be the same, but may need to be directed specifically towards each individual patient.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Miao
authors.affiliation: Division of Allergy and Immunology, Thomas Jefferson University, Nemours/A.I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19810 USA. Electronic address: cchang@nemours.org.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chang
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616 USA. Electronic address: megershwin@ucdavis.edu.
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. Electronic address: maxiongmd@hotmail.com.
authors.forename: Xiong
authors.initials: X
authors.lastname: Ma
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017074:Common Variable Immunodeficiency / Q000453:epidemiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
keywords: Anti-mitochondrial antibodies; Autoimmunity; Hypogammaglobulinemia; Primary biliary cirrhosis; Specific antibody deficiency; T regulatory cells