BACKGROUND: Atherosclerosis is an inflammatory disease where oxidized low-density lipoprotein may play an important role through phosphorylcholine (PC)-exposing inflammatory phospholipids. Both atherosclerosis and its clinical consequence cardiovascular disease (CVD) are highly prevalent in patients with end-stage renal disease (ESRD). We here study the association between IgM antibodies against phosphorylcholine-A (anti-PC) and risk of death in patients undergoing haemodialysis (HD). METHODS: We performed a prospective observational study examining the relationship between anti-PC concentrations and mortality risk in a well-characterized cohort of 203 prevalent HD patients [56% men, median age 66 (interquartile range 51-74) years, vintage time 29 (15-58) months] with a mean follow-up period of 29 (14-58) months. RESULTS: Median anti-PC levels were lower in HD patients with systemic collagen vascular disease (18.9 versus 45.2 U/mL, P = 0.01) and in patients who died during the follow-up period (29.5 versus 53.9 U/mL; P = 0.0008). The patients with an anti-PC value below the median (42.1 U/mL) had a higher mortality rate with a crude hazard ratio (HR) of 2.13 (95% CI 1.40-3.22). These patients remained at higher risk of death (HR 1.76; 95% CI 1.13-2.74) even after adjustment for traditional risk factors (age, sex, smoking habits, CKD aetiology, CVD and diabetes), protein-energy wasting and inflammation (HR 1.70; 95% CI 1.19-2.68). CONCLUSION: Low levels of natural IgM antibodies against PC are independent predictors of death among HD patients. Further studies are needed to define the clinical role of such measurements and to explore potentials for active immunization, with PC as an antigen, or passive immunization, aiming at raising levels of protective anti-PC.
BACKGROUND:Atherosclerosis is an inflammatory disease where oxidized low-density lipoprotein may play an important role through phosphorylcholine (PC)-exposing inflammatory phospholipids. Both atherosclerosis and its clinical consequence cardiovascular disease (CVD) are highly prevalent in patients with end-stage renal disease (ESRD). We here study the association between IgM antibodies against phosphorylcholine-A (anti-PC) and risk of death in patients undergoing haemodialysis (HD). METHODS: We performed a prospective observational study examining the relationship between anti-PC concentrations and mortality risk in a well-characterized cohort of 203 prevalent HDpatients [56% men, median age 66 (interquartile range 51-74) years, vintage time 29 (15-58) months] with a mean follow-up period of 29 (14-58) months. RESULTS: Median anti-PC levels were lower in HDpatients with systemic collagen vascular disease (18.9 versus 45.2 U/mL, P = 0.01) and in patients who died during the follow-up period (29.5 versus 53.9 U/mL; P = 0.0008). The patients with an anti-PC value below the median (42.1 U/mL) had a higher mortality rate with a crude hazard ratio (HR) of 2.13 (95% CI 1.40-3.22). These patients remained at higher risk of death (HR 1.76; 95% CI 1.13-2.74) even after adjustment for traditional risk factors (age, sex, smoking habits, CKD aetiology, CVD and diabetes), protein-energy wasting and inflammation (HR 1.70; 95% CI 1.19-2.68). CONCLUSION: Low levels of natural IgM antibodies against PC are independent predictors of death among HDpatients. Further studies are needed to define the clinical role of such measurements and to explore potentials for active immunization, with PC as an antigen, or passive immunization, aiming at raising levels of protective anti-PC.
Authors: Michael Sobel; Katherine I Moreno; Mayumi Yagi; Ted R Kohler; Gale L Tang; Alexander W Clowes; Xiao-Hua A Zhou; Evercita Eugenio Journal: J Vasc Surg Date: 2013-07-13 Impact factor: 4.268
Authors: A G Frostegård; X Hua; J Su; J J Carrero; O Heimbürger; P Bárány; P Stenvinkel; J Frostegård Journal: Clin Exp Immunol Date: 2013-12 Impact factor: 4.330
Authors: Cristina Anania; Thomas Gustafsson; Xiang Hua; Jun Su; Max Vikström; Ulf de Faire; Mikael Heimbürger; Tomas Jogestrand; Johan Frostegård Journal: Arthritis Res Ther Date: 2010-11-23 Impact factor: 5.156