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Objective  Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies, including seropositivity for rheumatoid factor (RF) and anti–citrullinated protein antibodies (ACPAs). In addition, antibodies to carbamylated proteins (anti‐CarP) are present in patients with RA and are associated with joint damage. This study was undertaken to assess the presence of anti‐CarP antibodies in indigenous North Americans (First Nations [FN] populations) with RA compared to their at‐risk first‐degree relatives (FDRs) and healthy controls.    Methods  Anti‐CarP IgG and ACPAs (specifically, anti–cyclic citrullinated peptide [anti‐CCP] antibodies) were measured by enzyme‐linked immunosorbent assay in the sera of FN patients with RA (n = 95), their unaffected FDRs (n = 109), and healthy FN controls (n = 85). Antibodies to additional citrullinated peptides were measured using a multiplex ACPA array, and the number of peptides recognized was reported as an ACPA score. Groups were compared using the chi‐square test and Mann‐Whitney U test. Associations between RA and seropositivity for RF, ACPAs, and anti‐CarP antibodies were determined by logistic regression.    Results  Anti‐CarP antibodies were more frequent in FN patients with RA (44.3%) compared to FDRs (18.3%) and FN controls (4.7%) (both  P  &lt; 0.0001 versus RA). Moreover, anti‐CarP antibodies were more frequent in FDRs than in FN controls ( P  = 0.008). The ACPA score was higher in anti‐CCP–positive FN patients with RA than in anti‐CCP–positive FN FDRs (median score 7 [interquartile range (IQR) 7] versus median score 1 [IQR 4];  P  = 0.04). The association with RA was strongest when all 3 autoantibodies (RF, anti‐CCP, and anti‐CarP) were present in the patients’ serum (odds ratio 194, 95% confidence interval 23–1,609,  P  &lt; 0.0001).    Conclusion  Anti‐CarP antibodies are prevalent in FN patients with RA and also more common in their at‐risk FDRs compared to healthy controls. The results indicate an association of RF, ACPAs, and anti‐CarP with RA that is strongest when all 3 autoantibodies are present. These findings may provide new insights into the evolution of autoimmunity in preclinical RA.

arthritis and rheumatology

Role of Anti–Carbamylated Protein Antibodies Compared to Anti–Citrullinated Protein Antibodies in Indigenous North Americans With Rheumatoid Arthritis, Their First‐Degree Relatives, and Healthy Controls