Potential roles of activation-induced cytidine deaminase in promotion or prevention of autoimmunity in humans

Abstract

Autoimmune manifestations are paradoxical and frequent complications of primary immunodeficiencies, including T and/or B cell defects. Among pure B cell defects, the Activation-induced cytidine Deaminase (AID)-deficiency, characterized by a complete lack of immunoglobulin class switch recombination and somatic hypermutation, is especially complicated by autoimmune disorders. We summarized in this review the different autoimmune and inflammatory manifestations present in 13 patients out of a cohort of 45 patients. Moreover, we also review the impact of AID mutations on B-cell tolerance and discuss hypotheses that may explain why central and peripheral B-cell tolerance was abnormal in the absence of functional AID. Hence, AID plays an essential role in controlling autoreactive B cells in humans and prevents the development of autoimmune syndromes.

Keywords::

• Primary immunodeficiency
• class switch recombination-deficiency
• tolerance

Acknowledgements

This work was funded by grants from Institut National de la Santé et de la Recherche Médicale, the European Union's 7th RTD Framework Programme (EUROPAD contract 201549 and PID-IMMUNE contract 232809), Association Contre Le Cancer, ANR Blanc 2010-CSRD. This work was also supported by Grant Number AI061093, AI071087, AI082713 and AI095848 from NIH-NIAID (to E. M.). Tineke Cantaert was funded by a Rubicon grant from the Netherlands Organization for Scientific Research (NWO). S. K. is a scientist from the french Centre National de la Recherche Scientifique (CNRS).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.