title: Circulating regulatory T cells in patients with aortic valve stenosis: Association with disease progression and aortic valve intervention.
abstract: BACKGROUND
  Severe aortic valve stenosis (AS) accounts for considerable morbidity and death, especially in older patients. There is increasing evidence to suggest a role for immune modulating cells in aortic valve (AV) degeneration. Regulatory T cells (Tregs) tune down inflammation. We aimed to study the levels of circulating Tregs in patients with AS and to assess their association with disease progression.
  
  
  RESULTS
  The number of Tregs (CD4+CD25+Foxp3+) was determined by flow cytometry in 229 patients with AS and a control group of 69 patients. Tregs were significantly higher in patients with AS compared to the control group (1.64± .61% vs 1.13±0.97%, p=0.04). In the logistic regression analysis, adjusted for baseline characteristics, only the hemoglobin level and Treg percent correlated with the presence of AS (OR 0.642 95% CI 0.512-0.805, p<0.001 and OR 1.411, 95% CI 1.080-1.844, p=0.011, respectively). One hundred patients underwent 2 echocardiographic studies during follow-up. The median decrease in AV area (AVA) was 0.1cm(2)/year. A borderline association was observed between Tregs and AVA progression (r=0.19, p=0.054). In a subgroup of 68 patients with severe AS, the association between Tregs and AVA progression was significant (r=0.374, p=0.0017). In addition, a drop in Treg levels was observed 3-6months after AV-intervention (1.86±1.6% vs 1.04±1.8%, p=0.0005).
  
  
  CONCLUSIONS
  Circulating Tregs are elevated in patients with AS. The levels of Tregs are higher in patients with severe AS and accelerated progression of valve narrowing. These results may help to identify AS patients with accelerated disease progression and possibly in need for earlier intervention.
authors.affiliation: The Heart Institute, Kaplan Medical Center, Rehovot, Israel. Electronic address: Sara_s@clalit.org.il.
authors.forename: Sara
authors.initials: S
authors.lastname: Shimoni
authors.affiliation: The Heart Institute, Kaplan Medical Center, Rehovot, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Bar
authors.affiliation: The Heart Institute, Kaplan Medical Center, Rehovot, Israel.
authors.forename: Valery
authors.initials: V
authors.lastname: Meledin
authors.affiliation: The Heart Institute, Kaplan Medical Center, Rehovot, Israel.
authors.forename: Gera
authors.initials: G
authors.lastname: Gandelman
authors.affiliation: The Heart Institute, Kaplan Medical Center, Rehovot, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000276:immunology / Q000601:surgery*; D018450:Disease Progression; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000379:methods*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
keywords: Aortic valve stenosis; Immune system; Progression; Regulatory T cells