Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Other |
Demonstration of the impact of CHIP on single-cell transcriptomics of arterial wall-infiltrating leukocytes |
Arterial wall Cluster of Differentiation (CD) 45+ leukocytes will be isolated after digestion of arterial tissue and characterized by single-cell transcriptomics, with a specific focus on wall infiltrating T cells and macrophages and their subsets (eg: Vascular dendritic cells, Th1, Th2, Th17, Treg, M1- and M2-like,…). Frequencies of these subsets and their genetic expression will be compared between wall-infiltrating leukocytes from GCA patients with or without CH, focusing on events supposed to be pathogenic in GCA, or known to be dysfunctional in CHIP: cytokine production, inflammasome activation and apoptosis, lymphocyte exhaustion, neoangiogenesis, tissue remodeling (fibrosis or matrix protease production), mitochondrial function and production of reactive oxygen species (ROS), neoangiogenesis, T-Cell receptor and B-cell receptor and costimulatory pathways. |
From 11th month of study to 18th month |
|
Primary |
Correlation of GCA with M-CHIP-driven by DNMT3A mutations |
Patients with M-CHIP will be identified by whole exome sequencing from the peripheral blood. The prevalence of DNMT3A-driven M-CHIP will be compared in the GCA patients vs matched controls by Chi-squared test or Fisher test. |
From beginning of study for 11 months |
|
Secondary |
Correlation of GCA with M-CHIP-driven by TET2, ASXL1 and JAK2 mutations |
Patients with M-CHIP will be identified by whole exome sequencing from the peripheral blood. The prevalence of TET2, ASXL1 or JAK2-driven M-CHIP will be compared in the GCA patients vs matched controls by Chi-squared test or Fisher test. |
From beginning of study for 11 months |
|
Secondary |
Correlation of GCA with L-CHIP-driven by DUSP22, FAT1 and KMT2D mutations |
Patients with L-CHIP will be identified by whole exome sequencing from the peripheral blood. The prevalence of DUSP22, FAT1 or KMT2D-driven L-CHIP will be compared in the GCA patients vs matched controls by Chi-squared test or Fisher test. |
From beginning of study for 11 months |
|
Secondary |
Correlation of GCA with M-CHIP and L-CHIP clone dimension |
Patients with M-CHIP or L-CHIP will be characterized for the dimension of the mutated clone in the peripheral blood by assessing the Variant Allele Fraction (VAF) at whole exome sequencing. The VAF will be compared between the GCA group and the matched controls by an unmatched non-parametric test (Mann-Whitney U test). |
From beginning of study for 11 months |
|
Secondary |
Correlation of GCA with M-CHIP and L-CHIP multiple mutations |
The prevalence of M-CHIP and L-CHIP driven by multiple mutations as assessed by whole exome sequencing will be compared between the GCA group and the matched controls by Chi-squared test or Fisher test. |
From beginning of study for 11 months |
|
Secondary |
Correlation of ischemic features in GCA with specific CHIP mutations |
The prevalence of specific CHIP mutations (assessed and defined as above) will be compared between GCA patients with vs without ischemic features (claudicatio mandibularis, soft tissue necrosis, ischemic optic neuropathy) by Chi-squared test or Fisher test. |
From beginning of study for 11 months |
|
Secondary |
Correlation of ischemic features in GCA with CHIP clone dimension |
The clone dimension as assessed by VAF (see above) will be compared between GCA patients with vs without ischemic features by the Mann-Whitney U test. |
From beginning of study for 11 months |
|
Secondary |
Correlation of rate of complications with specific CHIP mutations |
GCA patients will be followed prospectively; the prevalence of specific CHIP mutations (assessed and defined as above) will be compared between GCA patients with vs without complications at 12 months (disease relapse, venous thromboembolism, acute coronary syndromes/strokes, infection) by Chi-squared test or Fisher test. |
From patients' enrollment for 12 months |
|
Secondary |
Correlation of rate of complications with CHIP clone dimension |
GCA patients will be followed prospectively; the clone dimension as assessed by VAF (see above) will be compared between GCA patients with vs without complications at 12 months (disease relapse, venous thromboembolism, acute coronary syndromes/strokes, infection) by the Mann-Whitney U test. |
From patients' enrollment for 12 months |
|
Secondary |
Correlation of vascular quantitative score in GCA with specific CHIP mutations |
The prevalence of specific CHIP mutations (assessed and defined as above) will be compared between GCA patients with vs without incidence of large vessel involvement and burden of arterial stenosis and dilatation using quantitative activity scores such as Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI), using the Mann-Whitney U test. |
From beginning of study for 11 months |
|
Secondary |
Correlation of vascular quantitative score in GCA with CHIP clone dimension |
The clone dimension as assessed by VAF (see above) will be compared between GCA patients with incidence of large vessel involvement and burden of arterial stenosis and dilatation using quantitative activity scores such as Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI), using Spearman's rank correlation coefficient. |
From beginning of study for 11 months |
|
Secondary |
Correlation of histologic features in GCA with specific CHIP mutations |
The prevalence of specific CHIP mutations (assessed and defined as above) will be compared between GCA patients with histologic features such as intimal hyperplasia, fragmentation of internal elastic membrane, transmural inflammation, vasa-vasorum neoangiogenesis, and presence of giant cells by Chi-squared test or Fisher test. |
From beginning of study for 11 months |
|
Secondary |
Correlation of histologic features in GCA with CHIP clone dimension |
The clone dimension as assessed by VAF (see above) will be compared between GCA patients with histologic features such as intimal hyperplasia, fragmentation of internal elastic membrane, transmural inflammation, vasa-vasorum neoangiogenesis, and presence of giant cells, by the Mann-Whitney U test. |
From beginning of study for 11 months |
|