The crossroads of autoimmunity and immunodeficiency: Lessons from polygenic traits and monogenic defects  Bodo Grimbacher, MD, Klaus Warnatz, MD, Patrick F.K. Yong, MBChB, Anne-Sophie Korganow, MD, Hans-Hartmut Peter, MD  Journal of Allergy and Clinical Immunology  Volume 137, Issue 1, Pages 3-17 (January 2016) DOI: 10.1016/j.jaci.2015.11.004 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Monogenic defects and autoimmunity. Autoimmune expression of monogenic PIDs allows determination of major pathophysiologic pathways. Breakdown of central B-cell tolerance is required for the emergence of ANA-positive cells in patients with SLE, and deficiency of early complement components can be part of the pathogenesis. Treg cell dysregulation and/or activation of T cells, as seen in patients with CTLA4, LRBA, or FAS deficiency, are associated with autoimmune cytopenia. Type I interferon overproduction, as documented in TREX1- or stimulator of interferon genes (STING)–deficient patients, can lead to severe vasculitis. Mutations in AIRE or other defects of the thymus with impairment of negative T-cell selection through organ-specific autoantigen presentation leads to autoimmune endocrinopathies. Also, impairment in thymic Treg cell function, as in patients with IPEX syndrome, is associated with organ-specific autoimmunity. It is likely that organ characteristics influence the development of autoimmunity; another example is the exclusive joint and lung disease in patients with mutations in COPA. Journal of Allergy and Clinical Immunology 2016 137, 3-17DOI: (10.1016/j.jaci.2015.11.004) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions