Results from retrospective studies in Pre-RA cohorts have shown that both anti-cyclic-citrulline peptide antibodies (anti-CCP), other ACPA reactivities and increase of some inflammatory markers can precede RA diagnosis and/or symptom onset with a median time of 5–6 years (maximum 13–25 years) [5–8]. This evidence concerns the gene PRTN3 and rheumatoid arthritis.