Unraveling the Pleiotropic Role of High-Density Lipoproteins (HDLs) in Autoimmune Rheumatic Diseases.

Autoimmune rheumatic diseases (ARDs) exhibit an elevated incidence of cardiovascular disease (CVD). The elevation of inflammatory and immune stress accompanying ARDs contributes to atherosclerosis development and alterations in lipid metabolism and lipoprotein profile add to cardiovascular (CV) risk. The plasma concentration of high-density lipoprotein cholesterol (HDLc) is inversely related to CVD and serves as a discriminator of CV risk. However, this association is not unequivocal, and changes in HDL functionality appear to emerge as a better indicator of CV risk, albeit difficult to measure and monitor clinically. The modulation of HDLc itself can bring benefits in controlling autoimmunity and reducing ARD activity. Understanding HDL function and each peculiarity involved in ARDs enables to seek means to prevent ischemic outcomes associated with CVD, in the face of the residual CV risk persisting even with controlled disease activity and classic risk factors. By comprehending HDL's structural and functional nuances, it will be possible to develop more effective strategies to manage the evolution and outcomes of ARDs. It is also necessary to standardize diagnostic methods and establish different markers for each specific disease allowing the design of intervention strategies to restore HDL functionality, reduce residual CV, and prevent, alleviate, or even suppress ARD activity.