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Evol Med Public Health. 2018 Jan 12;2018(1):2-12. doi: 10.1093/emph/eoy001. eCollection 2018.

Linking autoimmunity to the origin of the adaptive immune system.

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Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Institute for Evolution and Biodiversity, University of Münster, 48149 Münster, Germany.
Clinic of Obstetrics and Gynecology, St Franziskus Hospital, 59227 Ahlen, Germany.
Department of Obstetrics and Gynecology, University Hospital of Münster, 48149 Münster, Germany.


In jawed vertebrates, the adaptive immune system (AIS) cooperates with the innate immune system (IIS) to protect hosts from infections. Although targeting non-self-components, the AIS also generates self-reactive antibodies which, when inadequately counter-selected, can give rise to autoimmune diseases (ADs). ADs are on the rise in western countries. Why haven't ADs been eliminated during the evolution of a ∼500 million-year old system? And why have they become more frequent in recent decades? Self-recognition is an attribute of the phylogenetically more ancient IIS and empirical data compellingly show that some self-reactive antibodies, which are classifiable as elements of the IIS rather then the AIS, may protect from (rather than cause) ADs. Here, we propose that the IIS's self-recognition system originally fathered the AIS and, as a consequence of this relationship, its activity is dampened in hygienic environments. Rather than a mere breakdown or failure of the mechanisms of self-tolerance, ADs might thus arise from architectural constraints.


adaptive immune system; immune tolerance; innate immune system; natural autoantibodies; pregnancy; self-recognition

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