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Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients

Kaelsch, A-I., Peters, A., Buhl, B., Breedijk, A., Prem, K., Schmitt, W. H., Weiss, C., Heeringa, P., Kallenberg, C., Birck, R. & Yard, B. A., 2009, In : Autoimmunity. 42, 5, p. 467-474 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Anna-Isabelle Kaelsch
  • Anthea Peters
  • Birgit Buhl
  • Annette Breedijk
  • Katharina Prem
  • Wilhelm H. Schmitt
  • Christel Weiss
  • Peter Heeringa
  • Cees Kallenberg
  • Rainer Birck
  • Benito A. Yard

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. TNF alpha 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 TNF alpha production and IL-10 were significantly lower in patients. Addition of 1,25-(OH)(2) D3, ATRA or 9c-RA, blunted TNF alpha 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 TNF alpha was more effective in patients, vitamin D supplementation might be an additional therapeutical approach.

Original languageEnglish
Pages (from-to)467-474
Number of pages8
JournalAutoimmunity
Volume42
Issue number5
Publication statusPublished - 2009

    Keywords

  • ANCA associated systemic vasculitis, vitamin D, RXRB, TNF alpha, WEGENERS-GRANULOMATOSIS, ALPHA EXPRESSION, DENDRITIC CELLS, TNF-ALPHA, T-CELLS, IN-VIVO, D-3, 1,25-DIHYDROXYVITAMIN-D3, DIFFERENTIATION, INVOLVEMENT

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