78. Clonal Hematopoiesis Across the Age Spectrum in Patients with Systemic Vasculitis
Creators: name: Sikora1, Keith
name: Wells1, Kristina
name: Gutierrez-Rodrigues1, Fernanda
name: Jones1, Adrianna I.
name: Rankin1, Cameron
name: Bhavisha Patel1
name: Quinn1, Kaitlin
name: Young1, Neal
name: Grayson1, Peter C.
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Clonal hematopoiesis (CH) is characterized by somatic mutations in hematologic precursor cells leading to a survival advantage of a single clone. Incidence of CH increases with age in healthy people, but is also associated with increased risk for all-cause mortality and cardiovascular disease and influence myeloid IL-1b and IL-6 production. Small studies report increased prevalence of CH in various inflammatory diseases. To what extent age versus inflammation underlies these associations is unclear. In this study, vasculitis patients with giant cell arteritis (GCA), ANCA-associated vasculitis (AAV), or Takayasu’s arteritis (TAK) were screened for CH to determine the relationship between CH and vasculitis in a cohort of patients with vasculitis representing a wide age spectrum. <strong>Methods:</strong> Error-correcting targeted sequencing was used to screen participants for peripheral blood somatic variants in 40 genes related to CH. Patients with vasculitis (GCA, AAV, TAK) were studied in 2:1 age-matched design compared to healthy controls (HC). Variants were called if the variant allele fraction (VAF) &gt; 0.5% and if the variants were predicted to impair protein function. Logistic regression was used to assess associations of age and vasculitis with CH. Relative contribution of predictor variables was assessed using standardized beta coefficients. Clinical features were compared using Fisher’s exact test, Wilcoxon rank sum test, or logistic regression as appropriate. Correlation between clone size and clinical features was assessed by linear regression. <strong>Results:</strong> The prevalence of CH was 53.8% (28/52) in GCA, 34.8% (16/46) in AAV, 13.0% (9/69) in TAK, and 14.5% (12/83) in HC. Median age for GCA, AAV, TAK, and HC was 72 (range: 50-88), 60 (range: 19-77), 33 (range: 3-71), and 51 (range: 3-88) years, respectively. Using logistic regression modeling, age and vasculitis were independently associated with CH (Age: <em>B</em>=0.05, standardized <em>b</em>=0.96, p&lt;0.0001; Vasculitis: <em>B</em>=0.53, standardized <em>b</em>=0.46, p=0.004). Of the 109 somatic mutations identified, the most common affected genes were <em>DNMT3A</em> (n=69, 63%) and <em>TET2</em> (n=19, 17%). Vasculitis patients with CHIP had lower percent lymphocytes (17.7% vs 25.4%, p=0.03) and higher absolute neutrophil counts (6.0 vs 5.1 K/uL, p=0.04) in peripheral blood than those without CH. Adjusting for daily prednisone dose, the neutrophil-to-lymphocyte ratio was significantly associated with presence of CH (<em>B</em>=0.07, p=0.02). Among patients with mutations, clone size was positively associated with age (<em>B</em>=0.01, p=0.002) and monocyte count (<em>B</em>=0.83, p=0.01). <strong>Conclusion:</strong> Patients with vasculitis can harbor somatic mutations in bone marrow that are reflected in peripheral blood. There is a complex relationship between age, inflammation and CH. Age is 2.1x more strongly associated with CH than vasculitis, but each are independent contributors. CH is associated with skewing of peripheral blood counts towards myeloid lineages in patients with vasculitis. Mechanison how CH directly contributes to vasculitic pathogenesis and the effect of systemic inflammation on mutagenesis and clonal selection are areas of active investigation. <strong>Disclosures:</strong> None