Clinical Reviews in Allergy & Immunology

, Volume 45, Issue 2, pp 162–169

Tolerance and Autoimmunity in Primary Immunodeficiency Disease: a Comprehensive Review

Article

DOI: 10.1007/s12016-012-8345-8

Cite this article as:
Gupta, S. & Louis, A.G. Clinic Rev Allerg Immunol (2013) 45: 162. doi:10.1007/s12016-012-8345-8

Abstract

The immune system has evolved to respond to pathogens (nonself) and unresponsive to self-antigens (tolerance). During the development of T and B cells in the thymus and bone marrow, respectively, self-reactive T and B cells are deleted by a process of apoptosis (both T and B cells) and become unresponsive to self-antigen by receptor editing (for B cells). However, few self-reactive T cells are leaked into the periphery. A number of mechanisms are responsible to ensure that self-reactive T and B cells remain unresponsive to self-antigens. In the central tolerance, major mechanisms include apoptosis (for T cells) and receptor editing (for B cells), and in the peripheral tolerance, a major mechanism appears to be regulated by Treg cells. In T cell central tolerance, one of the most important molecules is a transcription factor, autoimmune regulator, which is selectively expressed in medullary thymic epithelial cells (mTECs) and constitutively regulates the transcription of hundreds of self-antigens in mTECs, thereby inducing central tolerance, negative selection, and Treg differentiation from some self-reactive thymocytes. Primary immunodeficiency diseases are a group of monogenic diseases where mutations of certain genes have resulted in the loss of central and/or peripheral tolerance. As a result autoimmunity and autoimmune diseases are common among patients with primary immunodeficiency diseases. Here, we have provided a comprehensive review of the mechanisms of central and peripheral tolerance and autoimmune manifestations and mechanisms of autoimmunity in primary immunodeficiency diseases.

Keywords

Treg IPEX APECED ALPS WAS CVID IgA deficiency AIRE STAT5b 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Programs in Primary Immunodeficiency and Aging and Jeffrey Modell Diagnostic Center for Primary Immunodeficiencies, Division of Basic and Clinical Immunology, Medical sciences I, C-240University of California at IrvineIrvineUSA

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