Clonal Hematopoiesis in Giant Cell Arteritis

Not yet recruitingOBSERVATIONAL
Enrollment

326

Participants

Timeline

Start Date

March 31, 2024

Primary Completion Date

March 31, 2028

Study Completion Date

March 31, 2031

Conditions
Giant Cell ArteritisTemporal ArteritisClonal Hematopoiesis of Indeterminate PotentialHorton DiseaseSystemic Vasculitis Primary
Interventions
DIAGNOSTIC_TEST

Temporal arterial biopsy

Collection of 30 ml of peripheral blood in ethylenediaminetetraacetic acid (EDTA) tubes performed at baseline, 6 months, 12 months and in case of flare before month 12. In addition, the temporal artery specimen (at least 5 mm in length) exceeding that used for clinical activity (at least 10 mm in length in accordance with current clinical recommendations) will be digested to use for research purposes (about protocols for collecting, processing, storing and sending biopsy, refer to Standard Operating Procedures, SOP).

DIAGNOSTIC_TEST

Whole exome sequencing

"Patients with CHIP will be identified and characterized by using whole exome sequencing from the peripheral blood samples. M-CHIP will be further characterized by:~i) clone dimension as defined by Variant Allele Fraction (VAF); ii) mutations in specific genes such as DNMT3A, Tet methylcytosine dioxygenase 2 (TET2), Additional Sex combs (ASXL1), or Janus kinase 2 (JAK2); iii) multiple mutations.~L-CHIP will be further characterized by:~i) clone dimension as defined by the VAF; ii) mutations in specific genes such as Dual Specificity Phosphatase 22 (DUSP22), FAT atypical cadherin 1 (FAT1), (Histone-lysine N-methyltransferase 2D (KMT2D); iii) multiple mutations; iv) co-occurrence of mutations heralding M- and L-CHIP."

DIAGNOSTIC_TEST

Single cell transcriptomics

The investigators will identify actively inflamed arterial biopsies from three treatment-naïve patients without CHIP, and three treatment-naïve patients with CHIP driven by the most relevant gene mutation. 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 histological events supposed to be pathogenic in GCA, or known to be dysfunctional in CHIP.

All Listed Sponsors
lead

ASST Fatebenefratelli Sacco

OTHER

NCT06244069 - Clonal Hematopoiesis in Giant Cell Arteritis | Biotech Hunter | Biotech Hunter