Linked Life Data

14714889

Source:http://linkedlifedata.com/resource/pubmed/id/14714889

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-1-12
pubmed:abstractText
Autoimmune diseases are characterized by inflammation and by the development and maintenance of antibodies and T lymphocytes against "self" antigens. Although the etiology of these diseases is unknown, they have a number of cellular and molecular mechanisms in common. Pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), are upregulated and activate the inflammatory process. Chemokines recruit and activate leukocytes to release proteases, including matrix metalloproteinases (MMPs). These proteases degrade proteins into remnant fragments, which often constitute immunodominant epitopes. Either by direct loading into major histocompatibility complex (MHC) molecules or after classical antigen uptake, processing and MHC presentation, these remnant epitopes are presented to autoreactive T lymphocytes. Also, posttranslationally modified remnant peptides may stimulate B cells to produce autoantibodies. This forms the basis of the "Remnant Epitopes Generate Autoimmunity" (REGA) model. We have documented evidences for this model in multiple sclerosis (MS), rheumatoid arthritis (RA) and diabetes, which are summarized here. Furthermore, three topics will be addressed to illustrate the importance of glycobiology in the pathogenesis of autoimmune diseases. In MS, gelatinase B or MMP-9 is a pathogenic glycoprotein of which the sugars contribute to its interactions with the tissue inhibitor of metalloproteinases-1 (TIMP-1) and thus assist in the determination of the enzyme activity. In RA, gelatinase B cleaves denatured type II collagen into remnant epitopes, some of which constitute immunodominant glycopeptides. This implies that immunodominant epitope scanning experiments should preferably be done with natural posttranslationally modified glycopeptides, rather than with unmodified (synthetic) peptides. Sugars can also be used as molecular probes to induce autoimmune diseases. One of the best examples is the induction of acute pancreatitis, insulitis and diabetes by streptozotocin. In addition, gelatinase B is upregulated in pancreatitis and cleaves insulin. The most efficient cleavage by gelatinase B leads to a major insulin remnant epitope.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2598
pubmed:author
pubmed:issnType
Print
pubmed:volume
535
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
69-77
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Remnant epitopes generate autoimmunity: from rheumatoid arthritis and multiple sclerosis to diabetes.
pubmed:affiliation
Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't