Antibodies Against Phosphorylcholine Among 60-Year-Olds: Clinical Role and Simulated Interactions

Shailesh Kumar Samal; Pritam Kumar Panda; Max Vikström; Karin Leander; Ulf de Faire; Rajeev Ahuja; Johan Frostegård

doi:10.3389/fcvm.2022.809007

Antibodies Against Phosphorylcholine Among 60-Year-Olds: Clinical Role and Simulated Interactions

Front Cardiovasc Med. 2022 Apr 11:9:809007. doi: 10.3389/fcvm.2022.809007. eCollection 2022.

Authors

Shailesh Kumar Samal¹, Pritam Kumar Panda², Max Vikström³, Karin Leander³, Ulf de Faire³, Rajeev Ahuja^{2

4}, Johan Frostegård¹

Affiliations

¹ Section of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden.
² Condensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden.
³ Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden.
⁴ Department of Physics, Indian Institute of Technology Ropar, Rupnagar, India.

Abstract

Aims: Antibodies against phosphorylcholine (anti-PC) are implicated as protection markers in atherosclerosis, cardiovascular disease (CVD), and other chronic inflammatory conditions. Mostly, these studies have been focused on IgM. In this study, we determined IgG, IgG1, and IgG2 anti-PC among 60-year-olds.

Methods: Based on a 7-year follow-up of 60-year-olds (2,039 men and 2,193 women) from Stockholm County, we performed a nested case-control study of 209 incident CVD cases with 620 age- and sex-matched controls. Anti-PC was determined using ELISA. We predicted the binding affinity of PC with our fully human, in-house-produced IgG1 anti-PC clones (i.e., A01, D05, and E01) using the molecular docking and molecular dynamics simulation approach, to retrieve information regarding binding properties to PC.

Results: After adjustment for confounders, IgG and IgG2 anti-PC showed some significant associations, but IgG1 anti-PC was much stronger as a protection marker. IgG1 anti-PC was associated with an increased risk of CVD below 33rd, 25th, and 10th percentile and of stroke below 33rd and 25th, and of myocardial infarction (MI) below 10th percentile. Among men, a strong association with stroke was determined below the 33rd percentile [HR 9.20, CI (2.22-38.12); p = 0.0022]. D05 clone has higher binding affinity followed by E01 and A01 using molecular docking and further have been confirmed during the course of 100 ns simulation. The stability of the D05 clone with PC was substantially higher.

Conclusion: IgG1 anti-PC was a stronger protection marker than IgG anti-PC and IgG2 anti-PC and also separately for men. The molecular modeling approach helps in identifying the intrinsic properties of anti-PC clones and atomistic interactions with PC.

Keywords: SAbPred; antibodies; immune system; molecular docking and dynamics; myocardial infarction; phosphorylcholine (PC); stroke.