The aim of the study was to assess the sensitivity of this methodology in distinguishing RA patients from HC and to evaluate of the reliability of precursor markers for RA (anti-PAD-4 antibodies) in subjects at high risk of disease development (defined as subjects “at-risk” of RA based on familial RA and/or serum anticitrullinated protein antibody (ACPA) positivity). This evidence concerns the gene PADI4 and rheumatoid arthritis.