Background Lipoproteins are considered to excess pleiotropic functions in inflammation and autoimmunity. Apolipoprotein (apo) A1 has been reported to associate with arthritis development and hypercholesterolemia with radiographic progression in patients with rheumatoid arthritis (RA). Although a higher risk for more destructive RA in the presence of anti-citrullinated protein antibodies (ACPA) is recognized, responses driving the joint damage and protective mechanisms that could inhibit the pathological process are not defined.
Objectives We hypothesized that radiological joint damage progression would be influenced by lipoproteins. We aimed firstly to explore association between lipoproteins and radiographic damage, and secondly, to investigate if this association was different in ACPA+ and ACPA- patients.
Methods In all, 114 patients with early RA were included, 68% women, 71% ACPA+, mean age 50.6 (11.2) years. Apolipoproteins and oxidized low-density lipoprotein (oxLDL) were assessed in baseline serum and at 3, 12, 24 and 60 month after RA diagnosis. Radiographs of hands and feet were taken at inclusion, 12, 24 and 60 months and scored by the Sharp-van der Heijde (SHS) method. There were no differences between ACPA+ and ACPA- patients by age, sex, initial treatment, baseline DAS28, levels of lipoproteins and SHS, but ACPA+ patients had a longer symptom duration at inclusion, mean 6.8 (3.1) months vs. 4.8 (3.3), p=0.002. Normal regression was performed with adjustments for age, sex and initial treatments. Constant effects were tested in the final analyses as interaction with time was not significant. Significant associations were assessed within ACPA stratum.
Results Higher apoA1 at inclusion was associated with lower SHS over 5 years, β=-0.204 (-0.400; -0.008), p=0.042. When stratified by ACPA status, this association was shown in ACPA+ patients, β=-0.237 (-0.456; -0.017), p=0.035, after additional adjustment for baseline disease duration, β=-0.207 (-0.421; 0.012), p=0.064. In ACPA- patients, association between baseline apoA1 and SHS overtime were not found, p=0.99. There was a trend for association between apoB/apoA1 at baseline and SHS over follow-up, β=0.351 (-0.055; 0.758), p=0.090.
Higher levels of apoA1 over 5 years were associated with lower SHS progression (ΔSHS = SHS 5 years – SHS inclusion), β=-0.004 (-0.006; -0.002), p<0.001. This association was confirmed in ACPA+ patients, β=-0.004 (-0.006; -0.001), p=0.002, but not in ACPA-, p=0.39. The result in ACPA+ stratum was unchanged after adjustment for disease duration, β=-0.004 (-0.006; -0.001), p=0.002. Further, a positive relationship was observed between apoB/apoA1 over 5 years and ΔSHS, β=0.002 (0.001; 0.003), p=0.006, also valid for ACPA+ patients, β=0.002 (0.001; 0.003), p=0.021, but not ACPA- patients, p=0.79. The finding in ACPA+ stratum was stable after adjustment for disease duration, β=0.002 (0.001; 0.003), p=0.016.
There were no significant associations between apoB and oxLDL and radiographic outcome, p>0.05.
Conclusions We observed associations between apolipoproteins and radiographic outcome in patients with early RA. Apolipoprotein A1 showed a protective effect for radiographic joint damage in ACPA positive patients. Further exploring role of apolipoproteins may contribute to the understanding of immune-specific pathways.
Disclosure of Interest None declared