It is very well documented that predisposed individuals havethe presence of ACPA antibodies few years before the development of RAdisease phenotype, and there is a progressive increment in the titers ofACPA antibodies in the serum of these individuals and higher ACPA titers areassociated with severe RA, thus having a diagnostic and phenotypicinfluence. This evidence concerns the gene PRTN3 and rheumatoid arthritis.