Document Detail


Autoantibodies to glutathione S-transferase theta 1 in patients with primary sclerosing cholangitis and other autoimmune diseases.
MedLine Citation:
PMID:  18242955     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Primary sclerosing cholangitis (PSC) is an enigmatic disorder with a suggested autoimmune basis. A variety of autoantigens have been suggested but no specific or highly directed epitope has been identified. To address this issue, we constructed a cDNA library from normal human choledochus and screened expressing clones with serum from a patient with PSC and inflammatory bowel disease (IBD). Based on this screening, glutathione S-transferase theta 1 (GSTT1) was identified as a potential autoantigenic target. To study the specificity of GSTT1, we determined immunoreactivity using a panel of 58 patients with PSC, with and without IBD, 57 patients with IBD, 31 patients with Hashimoto's thyroiditis, 30 patients with primary biliary cirrhosis (PBC), 20 patients with insulin dependent diabetes mellitus, 22 patients with autoimmune polyendocrine syndrome type I, 10 patients with systemic lupus erythematosus (SLE), 20 patients with Sjögren's syndrome, 12 patients with autoimmune pancreatitis, 28 patients with Addison's disease, 27 patients with Grave's disease, 17 with myasthenia gravis, and 118 healthy controls. Reactivity against GSTT1 was found with PSC and IBD as well as some patients with other autoimmune pathology, indicating that this population of antibodies is neither specific nor a sensitive serologic marker for PSC, but the frequency was clearly higher in autoimmune patients than controls. GSTT1-antibodies have been described in persons with GSTT1-null genotype and are suggested to develop as an alloimmune response to blood transfusions from GSTT1-positive donors or pregnancies with GSTT1-positive children. Therefore, two IBD patients with and 15 PSC patients without GSTT1-antibodies were genotyped for GSTT1 to investigate if the presence of GSTT1-antibodies was associated with the GSTT1-null genotype and possibly caused by an alloimmune response. Both IBD patients and three of the PSC patients were of the GSTT1-null genotype. We note that the frequency of GSTT1-antibodies in this study is more than 100-fold higher than the frequency described earlier in patients with autoimmune diseases. We also observe an increased frequency of GSTT1-antibodies in patients with autoimmune diseases compared to healthy controls. This increased frequency can be explained by an autoimmune phenotype which increases susceptibility to such autoantibodies, or by a high frequency of the GSTT1-null genotype in autoimmune disease.
Authors:
Brita Ardesjö; Caisa M Hansson; Carl E G Bruder; Fredrik Rorsman; Corrado Betterle; Jan P Dumanski; Olle Kämpe; Olov Ekwall
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-02-01
Journal Detail:
Title:  Journal of autoimmunity     Volume:  30     ISSN:  0896-8411     ISO Abbreviation:  J. Autoimmun.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-04-28     Completed Date:  2008-07-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8812164     Medline TA:  J Autoimmun     Country:  England    
Other Details:
Languages:  eng     Pagination:  273-82     Citation Subset:  IM    
Affiliation:
Department of Medical Sciences University Hospital, Research Department 2, Lab 21, Entrance 70, 3rd Floor, Uppsala University, SE-75185 Uppsala, Sweden. brita.ardesjo@medsci.uu.se
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Autoantibodies / blood*
Autoantigens / immunology
Autoimmune Diseases / blood,  genetics,  immunology*
Child
Child, Preschool
Cholangitis, Sclerosing / blood,  genetics,  immunology*
Female
Gene Library
Genotype
Glutathione Transferase / genetics*,  immunology*
Humans
Infant
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Autoantigens; EC 2.5.1.-/glutathione S-transferase T1; EC 2.5.1.18/Glutathione Transferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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