Linked Life Data

15140055

Source:http://linkedlifedata.com/resource/pubmed/id/15140055

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-5-13
pubmed:abstractText
Autoimmune diseases are characterized by chronic inflammation in target organs and immunoreactivity towards one or multiple autoantigens. Several potential mechanisms of tolerance breaking have been postulated, one being inflammation-associated events. We have investigated whether chlorination of an autoantigen can lead to disruption of self-tolerance. Chlorination of antigens might occur during inflammation via the granulocyte-specific, myeloperoxidase-catalysed conversion of hydrogen peroxide to hypochlorous acid (HOCl). HOCl, being a strong oxidant, reacts with proteins both within cellular phagosomes and in the immediate extracellular environment. By immunizing Lew.1AV1 rats with chlorinated or unmodified rat serum albumin (RSA), we could detect tolerance-breaking effects of chlorination. RSA is a systemic autoantigen in rat not inducing antibody production upon immunization in its unmodified form. Rats immunized with chlorinated RSA (RSA-Cl) developed high titres of immunoglobulin G (IgG) specific for RSA-Cl which cross-reacted with native RSA. T cells reactive with both RSA-Cl and RSA were detected by [(3)H]-thymidine incorporation. We hence speculated that immunological tolerance established for unmodified proteins, during certain circumstances such as inflammation, might be broken by induced protein chlorination. T cells specific for the chlorinated protein can confer help to B cells recognizing both the chlorinated and the native form of the protein, leading to the formation of high-affinity autoreactive antibodies and possibly autoimmune disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0300-9475
pubmed:author
pubmed:issnType
Print
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
458-63
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Alteration of an autoantigen by chlorination, a process occurring during inflammation, can overcome adaptive immune tolerance.
pubmed:affiliation
Rheumatology Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't