Abstract 6259: Cd4+Cd28Null are Associated with Body Mass Index And Presence of Carotid Plaques: Altered Immune System as a Link Between Obesity and Atherosclerosis?
Obesity represents a low-grade inflammatory condition and a risk factor for atherotrombotic diseases. The causative mechanisms of this association however are still largely unknown. We hypothesized that CD4+CD28null lymphocytes, senescent lymphocytes with strong pro-inflammatory properties, elevated in chronic autoimmune diseases and in acute coronary syndromes, might be involved in the association between expanded adipose tissue and atherosclerosis.
Material and methods We studied 57 subjects, without overt cardiovascular disease, cathegorized by body mass index (BMI) in 19 normal (N, BMI 20 –25), 18 overweight (OW, BMI 25–30) and 20 obese (O, BMI 30 – 40). We evaluated carotid atherosclerosis by defining a plaque as a thickness more than 1 mm, by carotid ultrasonography. CD4+CD28null frequency in peripheral blood was measured by flow-cytometry. Serum levels of hs-C-reactive protein (CRP) and leptin were also assessed. No differences were found in age, sex, lymphocyte count and total CD4+ cell frequency, among groups. In O CD4+CD28null cell frequency (median, range 7.9, 2.1–32.2%) was significantly higher than in OW (3.2, 0.3–18.1%; P<0.05) and N (1.8, 0.3–15.1%; P<0.001). Interestingly, levels of CD4+CD28null positively correlated with the presence of carotid plaques (R=0.34; P= 0.006) and were the only independent predictors of carotid plaque presence at multivariate analysis together with age and male gender. Conversely, the other biomarkers analysed were associated with BMI but not with carotid plaques; CRP levels were significantly higher in O (4.3, 2.1 mg/L-33.4) than in OW (1.4 mg/L, 0.4 –18.9) and N (1.8 mg/L, 0.15–5.5, all P<0.05). Leptin levels were higher in O (41.65 ng/ml;3.09 –91) than in OW (12.7 ng/ml;2–28.5) and in N (9.04 ng/ml;1.9 –29.4). Our study demonstrate an higher frequency of CD4+CD28null T cells in peripheral blood of obese subjects and a positive correlation between these cells and the presence of carotid plaques, suggesting that CD4+CD28null T cells could represent a link between obesity and the risk of atherothrombotic disease.