1.
Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients.
Kälsch, AI, Peters, A, Buhl, B, Breedijk, A, Prem, K, Schmitt, WH, Weiss, C, Heeringa, P, Kallenberg, C, Birck, R, et al
Autoimmunity. 2009;(5):467-74
Abstract
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.
2.
Antineutrophil cytoplasmic antibodies (ANCAs) in patients with inflammatory bowel disease show no correlation with proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme: a Singapore study.
Ooi, CJ, Lim, BL, Cheong, WK, Ling, AE, Ng, HS
Annals of the Academy of Medicine, Singapore. 2000;(6):704-7
Abstract
INTRODUCTION The pathogenic importance of antineutrophil cytoplasmic antibodies (ANCAs) in inflammatory bowel disease (IBD) is unclear and target antigen localisation studies may lend insight to the specific pathogenic mechanisms of IBD. In this pilot study, we looked at occurrence of ANCA in Asian IBD patients. In ANCA-positive samples, we analysed for the presence of target antigens i.e. proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme. MATERIALS AND METHODS This prospective study was carried out from July 1997 to February 1998. Sera were screened for ANCAs with indirect immunofluorescent test and tested with an enzyme immunoassay (ELISA) kit which provides a semi-quantitative assay for human IgG autoantibodies against 6 antigens: proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme. RESULTS A total of 75 patients were studied: 50 with IBD and 25 controls with functional bowel disease. Ten had Crohn's disease (CD) and 40 had ulcerative colitis (UC). There was no racial predilection among the Chinese, Malays or Indians. In CD, 1 was positive for cytoplasmic ANCA (cANCA) and 2 for perinuclear ANCA (pANCA). In UC, 4 were positive for pANCA, 15 for atypical perinuclear ANCA (apANCA) and 1 for cANCA. In the CD and UC population, the proportion positive for ANCA was 30% and 50%, respectively. There was no ANCA detected among the controls. Of those ANCA-positive IBD patients (n:23), only 1 demonstrated anti-myeloperoxidase antibodies. No antibodies were detected against the other 5 antigens tested. CONCLUSIONS This pilot Singapore study concludes that there is no significant ANCA association with proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme.