Immune dysregulation in many primary immunodeficiency syndromes leads to autoimmune disease manifestations
Mutations in various genes can lead to immunodeficiencies, as well as to autoimmunity
Specific knowledge of these genetic alterations and their pathophysiological consequences will enable the development of new therapeutic approaches
Knowledge of primary immunodeficiency syndromes will enable a better understanding of potential infection-related adverse events when DMARDs are used to treat rheumatic diseases
Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.
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The work of the authors is supported financially by the Deutsches Zentrum für Gesundheitsforschung (DZIF) (grants to R.E.S. and through the Helmholz Society to B.G.) and by the Deutsche Forschungsgemeinschaft (DFG): Clinical Research Group KFO 250 (grants to R.E.S.and T.W.). The work of B.G. is also supported by the Federal Ministry of Education and Research (BMBF) (grants 01E01303 and 01ZX1306F), the DFG (grants SFB1160 and GR1617-8) and the EU (E-rare programme).
The authors declare no competing financial interests.
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Schmidt, R., Grimbacher, B. & Witte, T. Autoimmunity and primary immunodeficiency: two sides of the same coin?. Nat Rev Rheumatol 14, 7–18 (2018). https://doi.org/10.1038/nrrheum.2017.198
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