Different subclasses and isotypes of antibodies against phosphorylcholine in haemodialysis patients: association with mortality

Abstract

Summary The risk of premature death is high among patients on haemodialysis (HD patients). We previously determined that immunoglobulin (Ig)M antibodies against phosphorylcholine (anti‐PC) are negatively associated with increased risk of cardiovascular disease (CVD), atherosclerosis, some autoimmune diseases and mortality among HD patients in this cohort. Here, we also study other subclasses and isotypes of anti‐PC in HD patients in relation to mortality, inflammation and gender. The study group is a cohort of 209 prevalent HD patients [median age = 66 years, interquartile range (IQR) = 51–74], vintage time = 29 months (IQR = 15–58; 56% men) with a mean follow‐up period of 41 months (IQR = 20–60). Fifty‐six per cent were men. We also divided patients into inflamed C‐reactive protein (CRP) > 5·6 mg/ml and non‐inflamed CRP. Antibody levels were determined by in‐house enzyme‐linked immunosorbent assay. IgG1 anti‐PC below median was significantly associated with increased all‐cause mortality (after adjustment for confounders: P = 0·02), while IgG, IgA and IgG2 anti‐PC were not associated with this outcome. Among non‐inflamed patients, IgM and IgG1 anti‐PC were significantly associated with mortality (P = 0·047 and 0·02). IgG1 anti‐PC was significantly associated with mortality among men (P = 0·03) and trending among women (P = 0·26). IgM (as previously reported) and IgG1 anti‐PC are negatively associated with survival among HD patients and non‐inflamed HD patients, but among inflamed patients there were no associations. IgG, IgA or IgG2 anti‐PC were not associated with survival in these groups and subgroups. Further studies are needed to determine if raising anti‐PC levels, especially IgM and IgG1 anti‐PC, through immunization is beneficial.

Potential natural immunization against atherosclerosis in hibernating bears

“…IgG1 and IgA anti-PC has similar properties as IgM anti-PC, associated with protection in atherosclerosis progress 29 . We have also reported that IgM and IgG1 anti-PC is associated with longevity in CKD 30 . Given the protection against arteriosclerosis in a dyslipidemic and uremic milieu we analyzed anti-PC and anti-MDA in paired summer (active state) and winter (hibernation) bear samples and report that anti-PC, especially IgA and IgG1 are strikingly high in hibernating bears in contrast to anti-MDA.…”

“…IgM anti-PC promote polarization of T regulatory cells, from atherosclerotic plaques, another immunomodulatory and anti-inflammatory property of anti-PC with direct relevance for the present study 33 . Moreover, IgG1, more than IgG2, anti-PC has protective properties associated with less atherosclerosis progress, less vulnerable plaques and mortality in CKD 29 , 30 , 34 and IgA anti-PC is associated with favorable atherosclerosis progress 29 . It is likely that IgA anti-PC also shares at least some of these protective properties with other anti-PC subclasses and isotypes but more studies on IgA anti-PC are warranted.…”

“…Antibody measurements. Bear antibody levels of IgM, IgG, IgG1, IgG2 and IgA anti-PC and anti MDA were determined by in-house ELISA as described previously 6,13,25,29,30 . The concentration of the antigen (used in each well was 10 μg/mL.…”

Antibodies against phosphorylcholine in hospitalized versus non-hospitalized obese subjects

“…In general, these findings have been confirmed by other researchers 20 – 25 , and extended to other chronic diseases as osteoarthritis 24 . Less is known about other subclasses and isotypes of anti-PC than IgM, even though we determined that IgG1, but not IgG2, shows comparable associations with protection as IgM, in atherosclerosis 13 , SLE 26 , and for mortality in CKD 11 .…”

“…Antibodies such as IgM, IgG1 and IgG2 to PC were determined by ELISA essentially as described previously 6 , 11 – 13 . Briefly, pooled serum from Sigma Aldrich (St Louis, MO, USA) was used as standard in each plate.…”