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).
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.
Cell-mediated immunity to VZV was determined by performing interferon-γ (IFNγ) enzyme-linked immunospot and intracellular cytokine flow cytometry measurements in 11 GCA and 15 PMR patients and in 26 age/sex-matched HCs.
The recently demonstrated disturbed distribution of B cells in GCA could be also relevant in the pathogenesis of the disease, possibly contributing to the enhanced IL-6 response.
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.
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.
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.
Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica.
The risk of GCA in HLA-DRB1*04 positive individuals homozygous for the FCGR2A-131R allele is increased almost six-fold compared with those with other FCGR2A genotypes who are HLA-DRB1*04 negative.
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.