RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19890026http://www.w3.org/2000/01/rdf-schema#comment"

Context

Autoimmune Addison's disease is thought to result from T cell mediated autoimmunity. Autoantibodies against the steroidogenic cytochrome P450 enzyme 21-hydroxylase (21OH) are found in most patients, and 21OH is therefore a likely target for antigen-specific T cells.

Objective

The aim was to study cellular immunity to 21OH and its associations with 21OH autoantibodies and human leukocyte antigen alleles in autoimmune Addison's disease.

Design/patients

Peripheral blood mononuclear cells were collected from 33 patients with autoimmune Addison's disease and 21 controls. Cellular proliferation and production of cytokines in response to stimulation with 21OH or 21OH-derived peptides were tested.

Results

Cellular proliferation (P = 0.0009) and secretion of interferon-gamma (P < 0.0001) in response to 21OH was significantly higher in patients compared to healthy controls and associated with the presence of 21OH autoantibodies (P = 0.0052). Furthermore, the 21OH-specific production of interferon-gamma was enhanced in the presence of 21OH autoantibodies. This effect was partially inhibited by antibodies against the Fc receptor for IgG, CD32. Moreover, mature dendritic cells proved superior to the other antigen-presenting cells in invoking cellular responses to 21OH. An association between cellular immunity to 21OH and the high-risk HLA genotype for Addison's disease, DRB1*0301-DQ2/DRB1*0404-DQ8, was observed (P = 0.0089). Finally, a significant association between the DRB1*0404-DQ8 haplotype and cellular responses to a 21OH-derived peptide predicted to bind to DRB1*0404 was detected (P = 0.0055).

Conclusion

Patients with autoimmune Addison's disease have circulating 21OH-specific T cells, with amino acids 342-361 of 21OH possibly constituting a disease-specific epitope presented by HLA-DRB1*0404."xsd:string
http://purl.uniprot.org/citations/19890026http://purl.org/dc/terms/identifier"doi:10.1210/jc.2009-1115"xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/author"Bratland E."xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/author"Husebye E.S."xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/author"Undlien D.E."xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/author"Mozes E."xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/author"Skinningsrud B."xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/pages"5117-5124"xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/title"T cell responses to steroid cytochrome P450 21-hydroxylase in patients with autoimmune primary adrenal insufficiency."xsd:string
http://purl.uniprot.org/citations/19890026http://purl.uniprot.org/core/volume"94"xsd:string
http://purl.uniprot.org/citations/19890026http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19890026
http://purl.uniprot.org/citations/19890026http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19890026
http://purl.uniprot.org/uniprot/#_A0A0A7C3H3-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A0A7C3I1-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A0A7C3I5-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A0E3DC97-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A0E3DC99-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A076L4M5-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A0A0WDZ3-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A0A7C7I5-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A0A7C853-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026
http://purl.uniprot.org/uniprot/#_A0A0A7CAC7-mappedCitation-19890026http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19890026