We have previously demonstrated a distortion of self-reactive IgG antibody repertoires in patients with multiple sclerosis (MS) compared to controls, by immunoblotting assays, using human brain homogenates. The analysis of the immune profiles against human brain antigens allowed us to distinguish MS patients, and to associate a particular pattern of reactivity for each clinical form of MS. The aim of the present study was to evaluate the evolution of such patterns in patients with relapsing-remitting MS (RRMS). In a first step, we confirmed, by western blotting using human brains as source of antigens, the existence of specific repertoires of IgG reactivity in whole serum collected from healthy subjects (n = 32) and from untreated patients with RRMS (n = 56). In a second step, the evaluation of patterns was performed at baseline and 1 year later in untreated RRMS patients (n = 15), and in RRMS patients treated with IFN-beta (n = 41). In both groups, little change in IgG reactivity in whole serum was found. However, a higher degree of stability was noted in treated versus untreated patients (P < 0.01). Our results have showed a specific and relatively stable pattern of reactivity for each RRMS individual tested against brain antigens even after a 1-year treatment prevailing in treated patients suggesting that IFN-beta could stabilize IgG antibody repertoires.