Using MS, we found that the wild-type (WT) and mutant pilins were glycosylated between amino acids 67 and 75. Analyses by quantitative MS and high-pH anion exchange chromatography (HPAEC) revealed that the glycan in WT pilin is composed of xylose and fucose, whereas an additional sugar, rhamnose,
was found in the glycan of sll0899::Cm(r) Our findings suggest that an alteration in the O-linked glycan of pilin is responsible for the loss of pilus-mediated motility find more in sll0899::Cm(r).”
“BACKGROUND
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis.
METHODS
A genomewide association study was performed in a discovery cohort of 1233 U. K. patients with ANCA-associated vasculitis
and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria.
RESULTS
We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated selleck products vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated Ceramide glucosyltransferase with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2×10(-89), P = 5.6×10(-12), and P =
2.6×10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1×10(-8)).
CONCLUSIONS
This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.)”
“Background: Several standard venous assessment tools have been used as independent determinants of venous disease severity, but correlation between these instruments as a global venous screening tool has not been tested. The scope of this study is to assess the validity of Venous Clinical Severity Scoring (VCSS) and its integration with other venous assessment tools as a global venous screening instrument.