AI Article Synopsis

  • The study examined the role of antibodies against phosphorylcholine (anti-PC) in cardiovascular disease (CVD) among 60-year-olds, focusing on different types of antibodies, particularly IgG.
  • A nested case-control design was used, involving 209 CVD cases and 620 matched controls, and binding affinities of IgG1 anti-PC clones were predicted through advanced molecular techniques.
  • Results indicated that IgG1 anti-PC was a stronger protective marker against CVD risks compared to IgG and IgG2, especially notable in men, while molecular docking revealed the D05 clone showed the highest binding affinity to phosphorylcholine.

Article 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); = 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035555PMC
http://dx.doi.org/10.3389/fcvm.2022.809007DOI Listing

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Article Synopsis
  • The study examined the role of antibodies against phosphorylcholine (anti-PC) in cardiovascular disease (CVD) among 60-year-olds, focusing on different types of antibodies, particularly IgG.
  • A nested case-control design was used, involving 209 CVD cases and 620 matched controls, and binding affinities of IgG1 anti-PC clones were predicted through advanced molecular techniques.
  • Results indicated that IgG1 anti-PC was a stronger protective marker against CVD risks compared to IgG and IgG2, especially notable in men, while molecular docking revealed the D05 clone showed the highest binding affinity to phosphorylcholine.
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