The plenary session this morning began with Lillian Barra discussing the potential role of ACPA antibodies to the development of atherosclerosis in Rheumatoid Arthritis (RA). Patients with RA have a greater than 50% higher cardiovascular (CV) risk than the general population, and this elevated risk is not fully explained by traditional CV risk factors. Some believe that antibodies to citrullinated proteins could contribute to this increased CV risk.
Citrulline is a post-translational modification of arginine, which occurs in the presence of inflammation. There are citrullinated peptides found in atherosclerotic plaques of patients with cardiovascular disease. A new family of antibodies has been identified known as anti-carbamylated protein antibodies, or anti-homocitrullinated peptides (AHCPA). AHCPA are slightly different than ACPA, since they target homocitrulline rather than citrulline. It remains unclear whether this distinction is clinically relevant.
Research on cardiovascular pathogenesis has shown that homocitrullinated low-density lipoproteins (HcitLDL) are present in atherosclerotic plaque and enhance the formation of foam cells. Foam cells are macrophages that contain a high density of lipids and are important in the pathogenesis of atherosclerosis.
Dr. Barra's study found that LDLs can be homocitrullinated and citrullinated in vitro into HcitLDLs. They then went on to show that antibodies targeting HcitLDLs enhance the formation of foam cells, thereby increasing the development of atherosclerotic plaque. Finally, they found that humans with antibodies to ACPA had higher levels of antibodies targeting HcitLDL compared to healthy controls, thereby enhancing the formation of foam cells. This could potentially explain one mechanism by which patients with RA have higher risk of atherosclerotic disease and needs further investigation.
What is the clinical significance, you might ask? These findings could lead to the development of biomarkers to identify patients in whom we should target CV risk factors more aggressively. It is exciting to see Canadians continue to be on the forefront of research.
Dr. Jamal is a Clinical Associate Professor at the University of British Columbia and an active staff physician at Vancouver Coastal Health. Her interests include diagnosis and prognosis of early inflammatory arthritis, and timely assessment and access to care for patients with rheumatoid arthritis.View Full Bio