| Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients. | |
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MedLine Citation:
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PMID: 19811264 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It has been suggested that the retinoid X receptor beta (RXRB) gene is a risk factor for Wegener's granulomatosis. We addressed if there is a functional difference in the response to retinoic acid (RA) and vitamin D in Antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis (AASV) patients and if this was associated with RXRB genotypes. TNFalpha and IL-10 production were measured in whole blood assay from AASV patients (n = 51) and healthy controls (HC, n = 67). One micromolar of 1,25-(OH)(2) D3, 9-cis RA (9c-RA) or all-trans RA (ATRA) was added to the assay. Genotyping was performed for exons 7 and 2 of the RXRB gene and for a microsatellite in vicinity of the RXRB gene. Lipopolysaccharide (LPS) mediated TNFalpha production and IL-10 were significantly lower in patients. Addition of 1,25-(OH)(2) D3, ATRA or 9c-RA, blunted TNFalpha production, more pronounced in patients. Although all three compounds inhibited IL-10 production significantly in HC, only 1,25-(OH)(2) D3 was found to be effective in patients. Allele distribution of the RXRB microsatellite differed significantly between patients and HC. This was not found for the SNP in exons 2 and 7. Genotype of the latter correlated with the ability of 1,25-(OH)(2) D3 and ATRA to inhibit IL-10 production. We provide immunological evidence for a functional difference in vitamins D and A responsiveness in AASV patients. Since the inhibition of TNFalpha was more effective in patients, vitamin D supplementation might be an additional therapeutical approach. |
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Authors:
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Anna-Isabelle K??lsch; Anthea Peters; Birgit Buhl; Annette Breedijk; Katharina Prem; Wilhelm H Schmitt; Christel Weiss; Peter Heeringa; Cees Kallenberg; Rainer Birck; Benito A Yard |
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Publication Detail:
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Type: Clinical Trial; Journal Article |
Journal Detail:
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Title: Autoimmunity Volume: 42 ISSN: 1607-842X ISO Abbreviation: Autoimmunity Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-10-08 Completed Date: 2010-01-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8900070 Medline TA: Autoimmunity Country: England |
Other Details:
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Languages: eng Pagination: 467-74 Citation Subset: IM |
Affiliation:
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Fifth Department of Medicine, University Hospital Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany. anna-isabelle.kaelsch@med5.ma.uni-heidelberg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Antibodies, Antineutrophil Cytoplasmic / blood* Female Humans Interleukin-10 / metabolism Male Middle Aged Polymorphism, Genetic* Retinoid X Receptor beta / genetics* Systemic Vasculitis / genetics, immunology* Treatment Outcome Tumor Necrosis Factor-alpha / drug effects, metabolism Vitamin A* / administration & dosage, therapeutic use Vitamin D* / administration & dosage, therapeutic use Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Antineutrophil Cytoplasmic; 0/Retinoid X Receptor beta; 0/Tumor Necrosis Factor-alpha; 11103-57-4/Vitamin A; 130068-27-8/Interleukin-10; 1406-16-2/Vitamin D |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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