Protection mechanism of autoantibodies against ox-LDL in ACS patients

AIM The first aim was to clarify whether CCL5 and IL-18 are accompanied with autoantibodies against ox-LDL activity and T-lymphocyte immune drift in ACS patients. A secondary aim was to investigate the extent of different reperfusion therapeutic strategies to alleviate inflammation. METHODS The present investigation recruited 30 coronary angiography negative persons as ①control group (n=30), and studied a total of 60 consecutive unselected ACS patients divided into other two groups: ②early reperfusion (ER) group and ③Late reperfusion (LR, after 2 weeks) combinated group. All patients had coronary angiography and venous blood samples of all participants were drawn every morning from day 2 to 28 after admission. Detection index including: blood fat index (TC, TG, HDL-C, LDL-C and ox-LDL), inflammation index (CCL5, IL-18, IL-33, IL-5 and hs-CRP), Plasma Ig isotypes, and analysis of Th1 (CD4+IFNγ+), Th2 (CD4+IL4+) by flow cytometry. RESULTS ①Blood lipid fluctuation: The blood lipid levels (TC, TG, LDL and ox-LDL) of the control group had little change during the 4 weeks (P>0.05). Between the two different reperfusion strategies, there was no differences in improvement of blood lipids metabolism (P>0.05). ②Inflammatory cytokines dynamic state; CCL5 decreases in the ER group were demonstrated at day 8, but in the LR group not until day 14. IL-18 reached a maximum at day 8 in the ER group but peaked at day 12 in the LR group. IL-5 and IL-33 appeared at day 4 in the ER group but were seen at day 16 in the LR group. hsCRP decreased in the ER group at day 4 but not until day 14 in the LR group. ③T-lymphocyte immune drift state: Flow cytometry showed that T lymphocyte subsets: both in the ER group and the LR group, T-lymphocyte immune drift was the most significant in the first week. Th1 bias who was relieved markedly from the beginning of the second week in ER group and from the third week in LR group evolved eventually toward an almost equal value of Th1/Th2 in the two treatment groups at the fourth week. The results showed that the ER group produced more total IgA, IgE, and IgG1 in the first 2 weeks, but total IgG2a and IgM in the ER group were almost equal with that in the LR group. Importantly, significantly elevated IgG1 antibody of ox-LDL were demonstrated at the ER group in the first 2 weeks, but IgM antibody of ox-LDL did not demonstrate significant differences between the ER and the LR groups. ④Correlation analysis was performed for continuous variables and found that plasma concentration of CCL5 with IL-18, IL-33 with IL-5 had clear association (P<0.01). Multiple linear regression analysis showed that CCL5 and ox-LDL had positive relationships with hsCRP, but IL-33 and ox-LDL antibody maintained negtive predictors with hs-CRP. CONCLUSION Early reperfusion strategy significantly alleviates the additional risk of plaque vulnerability compared with late reperfusion treatment and efficacy of early reperfusion strategy maybe better than late reperfusion treatment