IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.

OBJECTIVE:Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD). METHODS:Among sixty-year olds from Stockholm County in Sweden, previously screened fo...

Full description

Bibliographic Details
Main Authors: Johan Frostegård, Jun Su, Sudhir Sing, Xiang Hua, Max Vikström, Karin Leander, Bruna Gigante, Ulf de Faire, Anna G Frostegård
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5400230?pdf=render
_version_ 1811235544759271424
author Johan Frostegård
Jun Su
Sudhir Sing
Xiang Hua
Max Vikström
Karin Leander
Bruna Gigante
Ulf de Faire
Anna G Frostegård
author_facet Johan Frostegård
Jun Su
Sudhir Sing
Xiang Hua
Max Vikström
Karin Leander
Bruna Gigante
Ulf de Faire
Anna G Frostegård
author_sort Johan Frostegård
collection DOAJ
description OBJECTIVE:Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD). METHODS:Among sixty-year olds from Stockholm County in Sweden, previously screened for cardiovascular risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified during a 5-year follow-up. Using a nested case-control design, 622 age- and sex-matched controls were selected. Odds ratios (OR) with 95% intervals (CI) were calculated by conditional logistic regression. IgM anti-OxPS was measured by ELISA. Phagocytosis of apoptotic Jurkat-cells by macrophages was studied by flow cytometry. RESULTS:Anti-OxPS levels were lower among cases (median (interquartile range): 80.7 (60.9-101.0 vs. 84.6 (65.8-109.6); p = 0.047); among men (76.6 (55.8-99.2) vs. 82.0 (63.1-105.1); p = 0.022) and among women 89.6 (72.3-110.1) vs. 89.8 (69.9-114.4); p = 0.79). After adjustment for smoking, BMI, diabetes mellitus type II, hypercholesterolaemia and hypertension, and dividing into quartiles, using the highest quartile (quartile 4) as reference, quartile 3 was associated with a OR of 1.74 (CI 1.08-2.81). Quartiles 2 and 1 had similar associations, the later reaching statistical significance. Among men associations were stronger whereas no significant associations were observed in women. The OR of MI/angina comparing quartile 3 with quartile 4 was 2.31 (CI 1.30-4.11). The OR for quartile 2 and 1, respectively, were similar as for quartile 3. Total IgM increased uptake of apoptotic cells, which was reversed if incubated with OxPS. CONCLUSIONS:IgM anti-OxPS is a novel potential protection marker for CVD, in particular in men. Increased phagocytosis of dying/dead cells could be one potential underlying mechanism.
first_indexed 2024-04-12T11:53:59Z
format Article
id doaj.art-a9d1e80ab00847d1a1260439fb26f7ab
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-04-12T11:53:59Z
publishDate 2017-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-a9d1e80ab00847d1a1260439fb26f7ab2022-12-22T03:34:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01124e017119510.1371/journal.pone.0171195IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.Johan FrostegårdJun SuSudhir SingXiang HuaMax VikströmKarin LeanderBruna GiganteUlf de FaireAnna G FrostegårdOBJECTIVE:Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD). METHODS:Among sixty-year olds from Stockholm County in Sweden, previously screened for cardiovascular risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified during a 5-year follow-up. Using a nested case-control design, 622 age- and sex-matched controls were selected. Odds ratios (OR) with 95% intervals (CI) were calculated by conditional logistic regression. IgM anti-OxPS was measured by ELISA. Phagocytosis of apoptotic Jurkat-cells by macrophages was studied by flow cytometry. RESULTS:Anti-OxPS levels were lower among cases (median (interquartile range): 80.7 (60.9-101.0 vs. 84.6 (65.8-109.6); p = 0.047); among men (76.6 (55.8-99.2) vs. 82.0 (63.1-105.1); p = 0.022) and among women 89.6 (72.3-110.1) vs. 89.8 (69.9-114.4); p = 0.79). After adjustment for smoking, BMI, diabetes mellitus type II, hypercholesterolaemia and hypertension, and dividing into quartiles, using the highest quartile (quartile 4) as reference, quartile 3 was associated with a OR of 1.74 (CI 1.08-2.81). Quartiles 2 and 1 had similar associations, the later reaching statistical significance. Among men associations were stronger whereas no significant associations were observed in women. The OR of MI/angina comparing quartile 3 with quartile 4 was 2.31 (CI 1.30-4.11). The OR for quartile 2 and 1, respectively, were similar as for quartile 3. Total IgM increased uptake of apoptotic cells, which was reversed if incubated with OxPS. CONCLUSIONS:IgM anti-OxPS is a novel potential protection marker for CVD, in particular in men. Increased phagocytosis of dying/dead cells could be one potential underlying mechanism.http://europepmc.org/articles/PMC5400230?pdf=render
spellingShingle Johan Frostegård
Jun Su
Sudhir Sing
Xiang Hua
Max Vikström
Karin Leander
Bruna Gigante
Ulf de Faire
Anna G Frostegård
IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.
PLoS ONE
title IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.
title_full IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.
title_fullStr IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.
title_full_unstemmed IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.
title_short IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.
title_sort igm antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60 year olds
url http://europepmc.org/articles/PMC5400230?pdf=render
work_keys_str_mv AT johanfrostegard igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds
AT junsu igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds
AT sudhirsing igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds
AT xianghua igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds
AT maxvikstrom igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds
AT karinleander igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds
AT brunagigante igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds
AT ulfdefaire igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds
AT annagfrostegard igmantibodiestooxidizedphosphatidylserineasprotectionmarkersincardiovasculardiseaseamong60yearolds