Abstract
ObjectiveTo determine levels of athero-protective IgM antibodies against phosphorylcholine in mothers and term-born normal or low birth weight infants.ApproachTwenty three mother-infant pairs were studied, of whom 16 infants were within the normal weight range for gestational age (NGA; 3652[504] g) and 7 were small for gestational age (SGA; birth weight: 2715[255] g), the latter <2SD below the Swedish reference data mean for normal fetal growth. All infants were born at term (mean±SD 40.5±1.1 weeks). Serum was available from 6 mothers with SGA and 14 with NGA infants. Participating mothers were aged 34.0±3.9 years (no difference between groups). Fourteen neonates were boys and seven were girls. Levels of anti-PC IgM were determined by ELISA.ResultsNeonatal IgM anti-PC levels were low (undetectable in 8 infants out of which 3 were SGA) with a median of 76[range 0–2.51] U/ml. Maternal IgM anti-PC levels were significantly higher (median 7198[range: 25.32–656.0]) U/ml) and the proportion of mothers in highest quartile (>75th percentile) was larger in mothers of NGA-infants (43%) vs. those of SGA-infants (0%, p = 0.032).ConclusionsIgM anti-PC levels are low at birth, which suggests that these antibodies do not play a “housekeeping” role in immune function during fetal life/development, but arise predominately on exposure to external antigens after birth. Furthermore, low maternal IgM anti-PC levels may play a role in placental insufficiency, contributing to poor fetal growth and a small-for-date baby. This preliminary observation may have implications for the future risk of atherosclerosis/cardiovascular disease development in pregnant women and their offspring.
Highlights
Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition characterized by the presence of activated immune competent cells, such as T-cells and monocytes/macrophages, in atherosclerotic plaques [1]
Maternal IgM anti-PC levels were significantly higher U/ml) and the proportion of mothers in highest quartile (.75th percentile) was larger in mothers of normal weight range for gestational age (NGA)-infants (43%) vs. those of small for gestational age (SGA)-infants (0%, p = 0.032)
IgM anti-PC levels are low at birth, which suggests that these antibodies do not play a ‘‘housekeeping’’ role in immune function during fetal life/development, but arise predominately on exposure to external antigens after birth
Summary
Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition characterized by the presence of activated immune competent cells, such as T-cells and monocytes/macrophages, in atherosclerotic plaques [1]. Phospholipids are highly diversified molecular species ubiquitously expressed in cellular membranes, circulating lipoproteins such as low-density lipoproteins (LDL), and certain pathogens. Phosphorylcholine (PC) has been long recognized as the dominant oxidation-related phospholipid neo-epitope, and is an integral part of the pro-inflammatory phospholipid moiety on oxidized LDL (OxLDL). Several independent studies have consistently linked low IgM anti-PC levels to the development of adult atherosclerosis and CVD [2]. We reported that low IgM anti-PC levels independently predict death and co-morbidity in acute coronary syndrome [3]. The CVDprotective mechanisms of anti-PC have been shown in mice to include anti-inflammatory [4] and anti-atheroslerotic properties [5], as well as perhaps inhibition of OxLDL uptake by macrophages [6,7] and inhibition of cell-death [8]. AntiPC antibodies have long been known to be anti-infectious [9]
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