Autoimmunity in Severe Combined Immunodeficiency (SCID): Lessons from Patients and Experimental Models

Article

DOI: 10.1007/s10875-007-9159-y

Cite this article as:
Milner, J.D., Fasth, A. & Etzioni, A. J Clin Immunol (2008) 28(Suppl 1): 29. doi:10.1007/s10875-007-9159-y

Abstract

Autoimmunity is observed in many immunodeficiencies and is thought to be mediated mainly by persistent infection. Severe combined immunodeficiency (SCID) is the most severe form of immunodeficiency and is also on occasion associated with autoimmune phenomena, usually in the form of the Omenn’s Syndrome phenotype. Recent studies both in human and mice shed light into the pathogenesis of these two seemingly different conditions occurring together. Central tolerance, which is in charge of elimination of autoreactive T-cell clones, is defective in SCID because of markedly reduced expression of Aire, a transcriptional regulator for the expression of tissue-specific antigens in the thymus. Peripheral tolerance is also markedly decreased in SCID because of several factors including the expansion of T-cell clones as a consequence of the lymphopenia observed in these condition as well as a diminished number of T regulatory (FOXP3+)cells, allowing autoreactive T cells to proliferate and infiltrate various organs in the body of SCID. It is thus of no surprise when both central and peripheral tolerance are impaired that autoimmunity can be observed in SCID.

Keywords

Autoimmunity immunodeficiency Omenn syndrome tolerance AIRE foxP3 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Laboratory of ImmunologyNational Institute of Allergy and Infectious Diseases, NIAID, NIHBethesdaUSA
  2. 2.Department of PediatricsGoteborg University and The Queen Silvia Children’s HospitalGothenburgSweden
  3. 3.Meyer Children’s HospitalThe Rappaport School of Medicine, TechnionHaifaIsrael

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