title: The crossroads of autoimmunity and immunodeficiency: Lessons from polygenic traits and monogenic defects.
abstract: Autoimmune and immunodeficiency diseases are outcomes of a dysfunctional immune system and represent 2 sides of the same coin. Multiple single-gene defects have been identified, resulting in rare diseases with features of both autoimmunity and immunodeficiency. On the other hand, more common autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, show a polygenic inheritance pattern. Not surprisingly, the genes implicated in single-gene disorders have also been shown to be linked to polygenic disorders. In this review article, we discuss the contribution of various immune system genes to common polygenic autoimmune disorders, as well as the pathophysiologic pathways and clinical features of monogenic defects that result in autoimmune disease. We also explore the hypotheses underlying the development of autoimmune disease and the overlap between immunodeficiency and autoimmunity.
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany. Electronic address: b.grimbacher@ucl.ac.uk.
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.affiliation: Department of Clinical Immunology, Frimley Park Hospital, Frimley, United Kingdom.
authors.forename: Patrick F K
authors.initials: PFK
authors.lastname: Yong
authors.affiliation: Department of Clinical Immunology, University Hospital Strasbourg, Strasbourg, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Korganow
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Hans-Hartmut
authors.initials: HH
authors.lastname: Peter
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D020412:Multifactorial Inheritance
keywords: Autoimmunity; B cells; T cells; primary immunodeficiency diseases