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.
Further, proinflammatory genes including TNF, LTA, LTB, CCR7, RUNX3, CD6, CD40LG, IL2, IL6, NLRP1, IL1B, IL18, IL21, IL23R and IFNG were hypomethylated in the cellular milieu of GCA arteries.
Although no definite boundaries exist, it may be suggested that the IL-6/Th17/IL-17 pathway primarily drives systemic inflammation while the IL-12/Th1/IFN-γ pathway dominates in vascular wall inflammation both in TAK and giant cell arteritis.
Since IFN-gamma plays a pivotal role in the pathogenesis of giant cell arteritis (GCA), a polygenic primary systemic vasculitis involving elderly people from Western countries, in the present study we analysed for first time the implication of three IFN-gamma receptor (IFNGR) 1 gene variants in the susceptibility to and clinical expression of GCA.
The article then explores the advantages and disadvantages of using TCZ when compared to other biologics approved in RA, sJIA and pJIA and finally looks ahead to the future and the emerging role of IL-6 and its blockade by TCZ as a treatment for giant cell arteritis (GCA), polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV).
Although no definite boundaries exist, it may be suggested that the IL-6/Th17/IL-17 pathway primarily drives systemic inflammation while the IL-12/Th1/IFN-γ pathway dominates in vascular wall inflammation both in TAK and giant cell arteritis.
Her medical history is relevant for refractory giant cell arteritis on long-term high-dose prednisolone and recent commencement of tocilizumab (interleukin-6 monoclonal antibody).
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.
In conclusion, IL-6 may contribute to the accumulation of CD4 T cells in GCA by supporting their proliferation and survival within the arterial wall through mechanisms that are independent of effects on local T reg expansion.
Inclusion criteria for the qualitative analysis were (1) <sup>18</sup>F-FDG PET used to assess the disease activity, (2) The use of the ACR criteria for the diagnosis of TAK, (3) No case mixed vasculitis (i.e., no giant cell arteritis), and (4) CRP concentration and clinical disease activity available.
While glucocorticoids are the mainstay of treatment for GCA, new breakthrough treatments such as tocilizumab (an anti-IL-6 receptor antibody) have shown great promise in causing disease remission and reducing the cumulative glucocorticoid dose.
Cytokine studies on a limited number of temporal artery biopsy specimens have shown that interferon-gamma is produced in GCA and not in PMR, suggesting that this cytokine may be crucial to the development of overt vasculitis.
A total of 130 consecutive 18F-FDG PET/CT scans performed during the disease course for evaluating disease activity in 15 GCA and 13 TAK patients were retrospectively examined by two nuclear physicians blinded to clinical data.
Three days of high-dose glucocorticoid treatment attenuates large-vessel 18F-FDG uptake in large-vessel giant cell arteritis but with a limited impact on diagnostic accuracy.
Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica.
To assess the potential protective role of proinflammatory cytokines in the development of ischemic events in GCA, we measured tissue expression (66 individuals) and/or circulating levels (80 individuals) of interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), and IL-6 in patients with biopsy-proven GCA.