Immune mechanisms and potential immunological treatment in atherosclerosis

Our immune system is an important and central part of the defence mechanisms of our body. It carries out various important functions such as protecting us from invading microorganisms, removing dead cells, and producing antibodies for future defence. For this, proper synchronization between the innate and adaptive immunity is required. Our innate immune system acts as the first line of defence by eliminating non-specifically various pathogens and by activating antigen-presenting cells (APCs) that inform B-cells and T-cells of the adaptive immune system. B-cells can exhibit more specific actions against pathogens by an intricately regulated production of antibodies directed against antigens expressed by the pathogens. T-cells can produce cytokines and chemokines to alarm the complete immune system recruiting immune cells such as natural killer cells, mast cells and neutrophils. The immune system can also produce antibodies against self-antigens (autoantibodies). Autoantibodies can have pathogenic effects that cause autoimmune diseases such as Systemic Lupus Erythematosis. Interestingly, it has been shown recently that autoantibodies can also have protective effects alleviating diseases such as lupus nephritis and atherosclerosis. This thesis focuses specifically on homeostatic functions of the human autoantibodies anti-phoshorylcholine (anti-PC) and anti-malondialdehyde (anti-MDA) and their prevalence in cardiovascular disease (CVD) and chronic kidney disease (CKD).

1. Study I: Investigates the role of anti-PC and anti-MDA antibodies in patients undergoing hemodialysis and explores the associations with all-cause mortality in both males and females, also their relation to inflammation.

2. Study II: Evaluates the potential of natural immunization in hibernating bears, tigers, and polar bears with respect to the levels of anti-PC and anti-MDA antibodies.

3. Study III: Evaluates the role of antibodies against anti-PC antibodies among 60-Year-Olds with its clinical role and simulated interactions.

4. Study IV: Investigates the role of anti-PC antibody levels in Covid-19 patients and also investigates the interaction of spike protein with phosphorylcholine by using an in silico approach.

List of scientific papers

I. Samal SK, Qureshi AR, Rahman M, Stenvinkel P and Frostegard J. Different subclasses and isotypes of antibodies against phosphorylcholine in haemodialysis patients: association with mortality. Clin exp Immunol. 2020;201:94.
https://doi.org/10.1111/cei.13441

II. Samal SK, Qureshi AR, Rahman M, Stenvinkel P and Frostegard J. Antibodies against Malondialdehyde in Haemodialysis Patients and Its Association with Clinical Outcomes: Differences between Subclasses and Isotypes. J Clin Med. 2020;9:753.
https://doi.org/10.3390/jcm9030753

III. Samal SK, Frobert O, Kindberg J, Stenvinkel P and Frostegard J. Potential natural immunization against atherosclerosis in hibernating bears. Sci Rep. 2021;11:12120.
https://doi.org/10.1038/s41598-021-91679-1

IV. Samal SK, Panda PK, Vikström M, et al. Antibodies Against Phosphorylcholine Among 60-Year-Olds: Clinical Role and Simulated Interactions. Frontiers in Cardiovascular Medicine. 2022; 9.
https://doi.org/10.3389/fcvm.2022.809007

V. Samal SK*, Busch M*, Panda KP, Kumar N, Timmermans S, Schurgers LJ, Reutelingsperger CR, Paassen PV*, Frostegård J*. Antibodies against phosphorylcholine are associated with less severe disease in COVID-19: clinical role and simulated interactions using In-silico methods. *Denotes equal author contribution. [Manuscript]