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Antibodies against Phosphorylcholine and Malondialdehyde during the First Two Years of Life
Divya Thiagarajan1, Susanna L Lundström2, Göran Pershagen1,3
1Institute of Environmental Medicine, Karolinska Institutet, SE 17177 Stockholm, Sweden.
Insights
Antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) develop differently in early life. IgM anti-PC rises slowly, while IgM anti-MDA is present at birth, suggesting distinct developmental pathways.
Area of Science:
- Immunology
- Pediatrics
- Proteomics
Background:
- Antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) are linked to protection against chronic inflammatory diseases like atherosclerosis.
- The early-life development of these crucial antibodies is not well understood.
Purpose of the Study:
- To investigate the developmental trajectories of IgM and IgG anti-PC and anti-MDA from birth to two years of age.
- To compare antibody development in children with maternal antibody levels.
- To analyze the peptide sequence variation in developing antibodies.
Main Methods:
- Longitudinal study measuring antibody titers via ELISA in mothers and their children (n=105) from pre-conception to 2 years postpartum.
- Proteomics de novo sequencing used to analyze antibody peptide sequences.
- Comparison of antibody levels and sequence variation between children and mothers.
Main Results:
- Children were born with low IgM anti-PC but detectable IgM anti-MDA.
- Both IgM anti-PC and anti-MDA increased by age 2, but IgM anti-PC remained lower than maternal levels.
- IgG anti-MDA reached maternal levels by 1 year, while IgG anti-PC reached them by 2 years.
- Early antibody development showed high peptide sequence variation, contrasting with adult-specific sequences.
Conclusions:
- IgM anti-PC develops more slowly than anti-MDA, potentially influenced by external factors and infections.
- Anti-MDA development appears primarily driven by preprogramming, initiating earlier than anti-PC.
- These findings highlight distinct developmental patterns for key antibodies in early life.
Abstract:
Abs against phosphorylcholine (anti-PC) and Abs against malondialdehyde (anti-MDA) may be protective in chronic inflammation, like atherosclerosis and cardiovascular disease. It is not known how they develop early in life. Ab titers were measured using ELISA in healthy women (n = 105; born into life study) and their children. Plasma samples were collected from the mothers before conception and from the children at birth as well as at 1 and 2 y after birth. Extracted Abs were compared using a proteomics de novo sequencing approach. It was observed that children were born with very low levels of IgM anti-PC, whereas IgM anti-MDA was present at birth. Both IgM anti-PC and anti-MDA increased during the first 2 y of life, but IgM anti-PC in contrast to IgM anti-MDA was still significantly lower than in the mothers. IgG anti-PC decreased after 1 y but reached similar levels as mothers' after 2 y, whereas IgG anti-MDA reached similar levels as mothers' already after 1 y. Proteomics peptide sequencing analysis indicated large peptide sequence variation without specific clone expression during the early stage of life compared with the adult stage for which specific peptide sequences dominated. IgM anti-PC levels develop much slower than anti-MDA and are still relatively low at 2 y. We hypothesize that anti-PC is developed by a combination of preprogramming and exposure to the external world, in which infectious agents may play a role. For anti-MDA, preprogramming is likely to play a major role and at an earlier stage than for anti-PC.
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