Antibodies against Phosphorylcholine and Malondialdehyde during the First Two Years of 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.

Potential natural immunization against atherosclerosis in hibernating bears

“…We interpreted this data as pointing to an important role played by environmental factors, especially the microbiome, but that genetic programs also may play a role. In contrast, anti-MDA was present at intermediate levels from birth and reached mothers' levels after 2 years 42 Of note, in this study, the bears were rather young (2-3 years) and the development of anti-PC during maturation in bears is not known. We cannot exclude that anti-PC is not fully developed at this age, and studies of anti-PC in older bears are warranted.…”

Higher levels of anti-phosphorylcholine autoantibodies in early rheumatoid arthritis indicate lower risk of incident cardiovascular events

“…The concept of autoimmune diseases suggests that autoantibodies are inherently pathogenic; however, some autoantibodies of innate “natural” immunity are protective, i.e., “protective autoimmunity.” Innate IgM autoantibodies could arise spontaneously without antigenic or microbial stimuli. These IgM autoantibodies are present in the circulation from birth [ 28 ], and they are also developed by exposure to the phospholipids, such as phosphorylcholine (PC) [ 29 ]. PC is present in apoptotic cells, and they act as enhancers of the inflammation underlying both atherosclerosis and autoimmunity [ 30 , 31 ].…”

“…Innate IgM autoantibodies could arise spontaneously without antigenic or microbial stimuli. These IgM autoantibodies are present in the circulation from birth [28], and they are also developed by exposure to the phospholipids, such as phosphorylcholine (PC) [29]. PC is present in apoptotic cells, and they act as enhancers of the inflammation underlying both atherosclerosis and autoimmunity [30,31].…”

Antibodies against Phosphorylcholine—Implications for Chronic Inflammatory Diseases

“…It is therefore likely that the environment plays a role, especially the microbiome. More research is needed to delineate which bacteria or even virus can promote anti-PC development [ 60 ].…”