Document Detail

Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients.
MedLine Citation:
PMID:  19811264     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Autoimmunity     Volume:  42     ISSN:  1607-842X     ISO Abbreviation:  Autoimmunity     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-10-08     Completed Date:  2010-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8900070     Medline TA:  Autoimmunity     Country:  England    
Other Details:
Languages:  eng     Pagination:  467-74     Citation Subset:  IM    
Fifth Department of Medicine, University Hospital Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany.
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MeSH Terms
Aged, 80 and over
Antibodies, Antineutrophil Cytoplasmic / blood*
Interleukin-10 / metabolism
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
Reg. No./Substance:
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

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