Background/Purpose:

High density lipoprotein (HDL) cholesterol efflux capacity measures how well HDL particles remove cholesterol from lipid-laden macrophages, such as those found in atherosclerotic plaques.  This function of HDL is an important predictor of cardiovascular (CV) risk, independent of traditional risk factors, and is impaired in RA.  Apolipoprotein A1 (apoA1) is the component of HDL that mediates cholesterol efflux.  Recently developed assays can measure citrullinated apoA1 (cit-apoA1) as well as antibodies against cit-apoA1 (anti-cit-apoA1) in human serum.  Our objective was to study whether cit-apoA1 and anti-cit-apoA1 in RA subjects was associated with impaired HDL efflux capacity.

Methods:

We performed this study in a prospective RA cohort based at a large academic center.  We focused on a subgroup of subjects who had HDL cholesterol efflux capacity and total apoA1 measured in a previous study.  Subjects were included in the subgroup if they experienced a reduction in inflammation between two consecutive years.  HDL cholesterol efflux capacity was measured using a cell based assay, and total apoA1 was measured in a clinical laboratory using standardized commercial methods.  For the present study, we measured cit-apoA1 and anti-cit-apoA1 at baseline.  Cit-apoA1 was measured using ELISA and anti-cit-apoA1 was measured using a multiplex bead assay.  To test the association between cit-apoA1 and HDL efflux capacity, we studied cit-apoA1 as a proportion to total apoA1 levels: (cit-apoA1)/(total apoA1).  We then constructed a linear regression model to examine the association between the proportion of cit-apoA1 with HDL efflux capacity at baseline, adjusted by age and gender.  Additionally, we tested the association between cit-apoA1 with HDL efflux capacity, and total apoA1 with HDL efflux capacity in separate linear regression models.  We constructed a linear regression model to study the association between the concentration of anti-cit-apoA1 with HDL efflux capacity at baseline, adjusted by age and gender.

Results:

The 90 subjects in the study had a mean age of 57.4 (SD 12.3), 90% were female, and 77.8% were anti-CCP positive.  A higher proportion of cit-apoA1 in the serum was associated with impaired HDL efflux capacity [β=-46.0 (SE 22.0), p=0.039]. While there was no association between the absolute concentration of cit-apoA1 with HDL efflux capacity (p=0.47), a higher level of total apoA1 was associated with better HDL efflux capacity [β=-2.0×10^-3 (SE 3.0×10^-4), p=<0.0001].  We found no significant association between the concentration of anti-cit-apoA1 and HDL efflux capacity [β=-3.0×10^-4 (SE 2.0×10^-4), p=0.136].    

Conclusion:

This study suggests that a higher proportion of citrullinated apoA1 is linked with impaired ability of HDL to remove cholesterol from lipid-laden macrophages.  Larger studies are needed to further investigate this relationship and its potential impact on cardiovascular risk in RA.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-between-hdl-cholesterol-efflux-capacity-citrullinated-apoa1-and-anti-citrullinated-apoa1-antibodies-in-rheumatoid-arthritis/