AB0056 NATURAL ANTIBODIES AGAINST PHOSPHORYLCHOLINE AND MALONDIALDEHYDE DURING THE FIRST TWO YEARS OF LIFE: IMPLICATIONS FOR RHEUMATIC DISEASE
Authors: D. Thiagarajan, S. Lundström, G. Pershagen, C. Almqvist Malmros, E. Andolf, A. Hedman, O. Berg, N. Oparina, J. Frostegård
Journal: Annals of the Rheumatic Diseases (2020)

Background: Antibodies against phosphorylcholine (anti-PC) have potentially protective properties in both atherosclerosis and rheumatic disease. IgM anti-PC could play a role in SLE being associated with protection, also in relation to atherosclerotic plaques and vulnerable plaques in SLE 1 and being a non-responder to biologics in RA. 1 We reported potential mechanisms by which anti-PC could be protective: 1:anti-inflammatory; 2: inhibits uptake of oxLDL in macrophages, 3: inhibits cell death. 1 4: anti-PC (and anti-MDA) increases clearance of human dead cells which could be of importance not especially in SLE; 2 5: anti-PC increases T regulatory cells in SLE-patients´ T cells from a low level and also in atherosclerosis, with implications for both conditions. 3 Also antibodies against malondialdehyde (anti-MDA) have interesting properties Objectives: It is not known how these antibodies develop early in life and what may cause low levels. The objective is to determine this. Methods: Antibodies were studied by ELISA in healthy pregnant women (n=105; Born into life study) and their newborn children. Women were recruited before conception. Informed consent, questionnaires from parents and plasma sample was collected from children at birth from cord blood, at 1-year and 2 years after birth. Extracted antibodies were compared using a proteomics de novo sequencing approach. Results: Children were born with very low levels of IgM anti-PC, while IgM anti-MDA was present at birth,. Both IgM anti-PC and anti-MDA increased during the first two years of life, but IgM anti-PC in contrast to IgM anti-MDA was still significantly lower than mothers´. IgG anti-PC decreased after 1 year, but reached similar levels as mothers´ after 2 years while IgG anti-MDA reached similar levels as mothers´ already after one year. Proteomics peptide sequencing analysis indicates large peptide sequence variation without specific clone expression during early stage of life compared to the adult stage for which specific peptide sequences dominated. Conclusion: IgM anti-PC levels develop much slower than anti-MDA and are still relatively low at 2 years. We hypothesize that anti-PC is developed by a combination of pre-programming and exposure to the external world, where infectious agents may play a role. For anti-MDA pre-programming is likely to play a major role and at an earlier stage than for anti-PC. References: [1]Frostegard J. Immunity, atherosclerosis and cardiovascular disease. BMC Med . 2013;11:117. [2]Rahman M, Sing S, Golabkesh Z, Fiskesund R, Gustafsson T, Jogestrand T, Frostegard AG, Hafstrom I, Liu A and Frostegard J. IgM antibodies against malondialdehyde and phosphorylcholine are together strong protection markers for atherosclerosis in systemic lupus erythematosus: Regulation and underlying mechanisms. Clin Immunol . 2016;166-167:27-37. [3]Sun J, Lundstrom SL, Zhang B, Zubarev RA, Steuer J, Gillgren P, Rahman M, Ajeganova S, Liu A and Frostegard J. IgM antibodies against phosphorylcholine promote polarization of T regulatory cells from patients with atherosclerotic plaques, systemic lupus erythematosus and healthy donors. Atherosclerosis . 2018;268:36-48. Disclosure of Interests: Divya Thiagarajan: None declared, Susanna Lundström: None declared, Göran Pershagen: None declared, Catharina Almqvist Malmros: None declared, Ellika Andolf: None declared, Anna Hedman: None declared, Oscar Berg: None declared, Nina Oparina: None declared, Johan Frostegård Grant/research support from: Unconditional competitive grant from Amgen, related only to PCSK9, not the topic of this abstract