| The X chromosome and the sex ratio of autoimmunity. | |
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MedLine Citation:
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PMID: 22155196 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The number of human conditions that are currently considered to be autoimmune diseases (AID) has been steadily growing over the past decades and it is now estimated that over 10million people are affected in the United States. One of the major shared features among AID is the predominance in the female sex which in some cases changes with the age at disease diagnosis. Numerous hypotheses have been formulated based on intuitive scientific backgrounds to justify this sex imbalance, i.e. sex hormones and reproductive factors, fetal microchimerism, other sex-related environmental factors, a skewing of the X-chromosome inactivation patterns, and major defects in sex chromosomes. Nevertheless, none of these hypotheses has thus far gathered enough convincing evidence and in most cases data are conflicting, as well illustrated by the reports on fetal microchimerism in systemic sclerosis or primary biliary cirrhosis. The present article will critically discuss the main hypotheses (loss of mosaicism, reactivation, and haploinsufficiency) that have been proposed based on findings in female patients with specific AID along with two additional mechanisms (X-chromosome vulnerability and X-linked polyamine genes) that have been observed in AID models. Further, recent data have significantly shifted the paradigm of X chromosome inactivation by demonstrating that a large number of genes can variably escape silencing on one or both chromosomes. As a result we may hypothesize that more than one mechanism may contribute to the female susceptibility to tolerance breakdown while the possibility that unknown factors may indeed protect men from AID should not be overlooked. |
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Authors:
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Carlo Selmi; Enrico Brunetta; Maria Gabriella Raimondo; Pier Luigi Meroni |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-3 |
Journal Detail:
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Title: Autoimmunity reviews Volume: - ISSN: 1873-0183 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101128967 Medline TA: Autoimmun Rev Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, CA, USA; Autoimmunity and Metabolism Unit, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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