B-201 Prevalence of Emerging Biomarkers in Seropositive and Seronegative Rheumatoid Arthritis Patients

Abstract

About 30% of rheumatoid arthritis (RA) patients are seronegative for rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies, underscoring the need for additional biomarkers to improve diagnostic sensitivity. Emerging biomarkers such as mutated citrullinated vimentin (MCV), citrullinated a-enolase peptide 1 (CEP-1), Sa, and carbamylated protein (CarP) have been proposed to enhance serologic detection. Biomarker results for RF, CCP, MCV, CEP-1, and CarP were analyzed in 35,678 subjects. Patients were categorized into four groups: RF–CCP– (n=23,439), RF+CCP– (n=2,453), RF–CCP+ (n=1,258), and RF+CCP+ (n=1,749). The prevalence and overlap of emerging biomarker positivity were compared across groups. Overall, 4,295 subjects (23%) had at least one positive biomarker. Among RF–CCP– patients, positivity rates were CarP 31%, MCV 26%, Sa 19.5%, and CEP-1 7.7%, with limited overlap between markers. In RF+CCP– patients, CarP (32%) and MCV (24%) were most frequent. RF–CCP+ patients showed higher reactivity for MCV (19%) and Sa (16%). In contrast, 92% of RF+CCP+ patients demonstrated multiple biomarker positivity, most often combinations involving MCV and Sa. Biomarker distributions differed significantly among RF/CCP-defined groups (p<0.001). Emerging biomarkers are differentially expressed across RA subgroups. Single biomarker positivity predominates in RF–CCP– patients, whereas multiple reactivities are characteristic of RF+CCP+ patients. These findings highlight the limited overlap yet complementary diagnostic value of emerging RA-associated biomarkers, supporting their role in improving the evaluation of seronegative RA.