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

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.809007

DOI=10.3389/fcvm.2022.809007

ISSN=2297-055X

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. We hereby study IgG, IgG1, IgG2 anti-PC among 60-year-olds.
Methods 
Based on a 7-year follow-up of 60-year-olds (2039 men, 2193 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 were determined by ELISA. We predicted the binding affinity of PC with our fully human, in-house produced IgG1 anti-PC clones (A01, D05 and E01) using 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 increased risk of CVD below 33rd, 25th, and 10th percentile and of stroke below 33rd, 25th, and for MI below 10th percentile. Among men strong association with stroke was determined below 33rd percentile (HR 9.20, CI (2.22-38.12). 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 D05 clone with PC was substantially higher. 
Conclusions
IgG1 anti-PC was a stronger protection marker than IgG anti-PC and IgG2 anti-PC, and also for men separately. Molecular modeling approach helps in identifying the intrinsic properties of anti-PC clones and atomistic interactions with PC.