Although other vasculitides, such as giant cell arteritis (GCA) or immunoglobulin A vasculitis, have not benefitted by the great advantage of the large-scale genetic analyses yet, some interesting associations have been recently suggested, such as the classical functional PTPN22 allele rs2476601 (rs2476601" genes_norm="26191">R620W) with GCA.
In the non-HLA region, we confirmed a key role for the functional PTPN22rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function.
The 4 separate studies in the current protocol focus on: the association of clinical picture of PMR/GCA with PET findings; the validity of 18F-FDG PET/CT scan for diagnosis of PMR/GCA compared with temporal artery biopsy; the prevalence of newly diagnosed malignancies in patients with PMR/GCA, or PMR-like syndrome, with the focus on diagnostic accuracy of 18F-FDG PET/CT scan compared with conventional workup (ie, chest X-ray/abdominal ultrasound); and the impact of disease process, and also steroid treatment on bone mineral density, body composition, and vasculitis/vascular stiffness in PMR/GCA patients.
DRB1*04 (OR, 1.9 [0.96 to 3.8]; P =.06), especially *0401 (OR, 2.8 [1 to 7.7]; P =.04), and DRB1*07 (OR, 2.3 [1.2 to 4.6]; P =.01) were more frequent in GCA than in PMR.
Sequence comparison among the allelic products identified in the GCA cohort demonstrated heterogeneity for the sequence polymorphism of the third hypervariable region (HVR), but homology for the polymorphic residues within the HVR2 of the HLA-DRB1 gene.
GCA seems to be associated with HLA DRB1*04 (regardless of the subtype) and this association appears to be accompanied by corticosteroid resistance, suggesting that genomic typing may be useful to identify patients eligible for early alternative treatment to corticosteroid drugs.
GCA incidence (n = 17 countries) was associated with population HLA-DRB1*04 allele frequency (P = 0.008; adjusted R(2) = 0.51 on univariable analysis, adjusted R(2) = 0.62 after also including latitude); latitude also made an independent contribution.
A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1(∗)04.
Conflicting HLA-DRB1 genotype results have been reported, and recent studies have shown that PMR and GCA have different expression of RANTES, TNFalpha microsatellite, and IL-6 promoter genetic polymorphisms.
[Extent and location of lesions in aorta and its main branches in patients with nonspecific aortoarteritis with various genotypes in the region of major histocompatibility complex].