Background/Purpose: Beta-2-glycoprotein-I(b2GPI), an apolipoprotein abundant in plasma, is readily expressed in human atherosclerotic plaque. Anti-b2GPI-IgA antibodies (Ab) have been previously reported in both rheumatoid arthritis (RA) patients and controls;they independently predicted cardiovascular events in general patients. We explored whether a-b2GPI-IgA presence predicted coronary plaque burden, its progression and potential interactions between a-b2GPI-IgA and inflammation on atherosclerosis load increase in RA.

Methods: One hundred-one participants with a baseline coronary computed tomography angiography (CCTA) underwent follow-up assessment within 83±3.6 months. Numbers of coronary segments with plaque andcumulative plaque stenosis were recorded.Coronary artery calcium (CAC) was quantified by the Agatston method. Subclasses (IgG, IgM and IgA) of a-b2GPI Ab, anticardiolipin-Ab and lupus anticoagulant were assessed at baseline and confirmed 12-weeks later, if positive. Serum interleukin-6 (IL-6) was measured at baseline, while CRP was assessed on every visit from baseline through follow-up. Multivariable robust linear regression models evaluated the effect of a-b2GPI-IgA presence onbaseline CACandCAC change. Negative binomial regression assessed plaque progression, defined as number of segments with new plaque or increase in stenosis of existing plaque.The effects of interactions between a-b2GPI-IgA and time-averaged CRP or baseline IL-6 on plaque progression were also explored.

Results: A-b2GPI-IgA was highly prevalent (34.7%) in contrast to other antiphospholipid-Ab subclasses (< 4%). Their presence predicted baseline CAC score independently of age, hypertension, statin use, and CRP [β=0.37 (0.04-0.71), p=0.029]. A-b2GPI-IgA further predicted CAC change [β=0.387 (0.06-0.71), p=0.019] and plaque progression [IRR=1.62 (1.03-2.56), p=0.039], independently of age, hypertension, time-averaged CRP, cumulative prednisone and methotrexate dose and duration of statin exposure. Similarly, Ab presence predicted incident CAC [OR=5.67 (1.10-29.23), p=0.038] as well as prevalent CAC progression [β=0.64 (0.02-1.26), p=0.044]. Notably, a-b2GPI-IgA moderated the effect of both time-averaged CRP and baseline IL-6 (Figure 1) on CAC change [p-interaction=0.01 and 0.017 respectively]; specifically, higher time-averaged CRP and higher baseline IL-6 promoted CAC progression only in a-b2GPI-IgA positive patients [β =0.47 (0.26-0.67), p< 0.001 and β=0.43 (0.05-0.81), p=0.028, respectively] but not negative ones [β=0.07 (-0.10-0.25), p=0.395 and β=-0.07 (-0.34-0.20), p=0.621, respectively].

Conclusion: A-b2GPI-IgA in RA independently contribute to higher baseline coronary atherosclerosis burden, accelerated plaque progression and remodeling, especially in the context of higher cumulative inflammation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/beta-2-glycoprotein-i-iga-antibodies-predict-coronary-plaque-burden-progression-and-moderate-the-effect-of-inflammation-on-atherosclerosis-in-rheumatoid-arthritis/