The dominating changes of combinations of anti-CCP2 antibodies with anti-VCP1 and anti-VCP2 or anti-HCP1 and anti-HCP2 when the pre-symptomatic individuals were compared with the patients with RA were that the triple-negative groups (anti-CCP2–, anti-VCP1–, anti-VCP2– or anti-CCP2–, anti-HCP1–, anti-HCP2–, respectively) were reduced from 61.8 % to 21.2 % and 61.2 % to 19.9 %, respectively (Fig. 4c–d). This evidence concerns the gene CYCSP52 and rheumatoid arthritis.