NDLI: AIRE deficiency in thymus of 2 patients with Omenn syndrome

Content Provider	PubMed Central
Author	Cavadini, Patrizia William, Vermi Facchetti, Fabio Fontana, Stefania Seiho, Nagafuchi Mazzolari, Evelina Anna, Sediva Marrella, Veronica Villa, Anna Fischer, Alain Notarangelo, Luigi D. Badolato, Raffaele
Copyright Year	2005
Abstract	Omenn syndrome is a severe primary immunodeficiency with putative autoimmune manifestations of the skin and gastrointestinal tract. The disease is caused by hypomorphic mutations in recombination-activating genes that impair but do not abolish the process of VDJ recombination, leading to the generation of autoreactive T cells with a highly restricted receptor repertoire. Loss of central tolerance in genetically determined autoimmune diseases, e.g., autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, is associated with defective expression by medullary thymic epithelial cells of AIRE, the transcription activator that induces thymic expression of tissue-specific antigens. Analysis of AIRE expression in the thymi of 2 Omenn syndrome patients and 1 SCID patient, by real-time RT-PCR and immunohistochemistry, demonstrated a profound reduction in the levels of AIRE mRNA and protein in patients as compared with a normal control subject. Lack of AIRE was associated with normal or even increased levels of keratin and lymphotoxin-β receptor mRNAs, while mRNAs of the self-antigens insulin, cytochrome P450 1a2, and fatty acid–binding protein were undetectable in thymi from immunodeficiency patients. These results demonstrate that deficiency of AIRE expression is observed in severe immunodeficiencies characterized by abnormal T cell development and suggest that in Omenn syndrome, the few residual T cell clones that develop may escape negative selection and thereafter expand in the periphery, causing massive autoimmune reactions.
Related Links	http://dx.doi.org/10.1172/JCI200523087
Starting Page	728
File Format	PDF
ISSN	00219738
Journal	Journal of Clinical Investigation
Issue Number	3
Volume Number	115
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2005-03-01
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Atypical Omenn Syndrome due to Adenosine Deaminase Deficiency

Mutations in CHD7 in patients with CHARGE syndrome cause T–B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome

The AIRE -230Y Polymorphism Affects AIRE Transcriptional Activity: Potential Influence on AIRE Function in the Thymus

Murine models of Omenn syndrome

RAG1 Reversion Mosaicism in a Patient with Omenn Syndrome

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

Decreased AIRE and promiscuous gene expression in thymus from Down syndrome individuals may explain predisposition to autoimmunity

Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome.

Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency

AIRE deficiency in thymus of 2 patients with Omenn syndrome

Similar Documents

Atypical Omenn Syndrome due to Adenosine Deaminase Deficiency

Mutations in CHD7 in patients with CHARGE syndrome cause T–B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome

The AIRE -230Y Polymorphism Affects AIRE Transcriptional Activity: Potential Influence on AIRE Function in the Thymus

Murine models of Omenn syndrome

RAG1 Reversion Mosaicism in a Patient with Omenn Syndrome

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

Decreased AIRE and promiscuous gene expression in thymus from Down syndrome individuals may explain predisposition to autoimmunity

Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome.

Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency

AIRE deficiency in thymus of 2 patients with Omenn syndrome