Insights from populations at risk for the future development of classified rheumatoid arthritis

Rheumatoid arthritis (RA) develops through a series of stages. In the seropositive subset of classified RA patients, a preclinical stage is present for years before the onset of clinically apparent disease. Relevant preclinical biomarkers include autoantibodies, alterations of lymphoid populations, elevated cytokines/chemokines, genetic/genomic factors, imaging studies, clinical findings, dietary and environmental biomarkers, cardiovascular disease risk assessment, microbiome analyses, and metabolomic changes. Identifying the population of asymptomatic subjects at sufficiently high risk for disease to be informative and representative of "preclinical patients" is a challenge. This article reviews the results of analyses that have been undertaken in these "at-risk" subjects.