Rheumatoid Factor Beyond Rheumatoid Arthritis: A Potential Marker of Cardiometabolic and Hepatic Risk

Abstract

Rheumatoid factor (RF), which is an autoantibody that is predominantly targeted at the Fc region in IgG, has been a key point of diagnosis and prognostication of rheumatoid arthritis (RA). There is, however, an emergent body of evidence that RF positivity, including in persons with preexisting autoimmune disease as well as asymptomatic seropositive persons, can indicate more global immune dysregulation with consequences of cardiometabolic and hepatic health. RF is involved in the development of circulating immune complexes, which increases inflammation through complement activation, Fc receptor interaction and cytokine release. These routes are becoming well-known mechanistic causes of cardiometabolic diseases, such as atherosclerosis, insulin resistance, metabolic syndrome, and heart failure. Similarly, the immune-complex deposition and chronic inflammatory signaling also play a role in hepatic injury, metabolic dysfunction-associated fatty liver disease (MAFLD) and fibrosis. The present review summarizes the existing information about the role of RF as a predictor and a possible mediator of cardiometabolic and hepatic dysfunction in chronic diseases. We searched scientific databases for epidemiologic relationships, possible biological pathways, and clinical implications for risk stratification and integrated care. RF could serve as an accessible biomarker of systemic inflammatory risk, complementing its traditional role in rheumatology and, within the framework of precision medicine, helping to guide early detection and preventive strategies across diverse clinical populations.