Serum IgG repertoire in clinically isolated syndrome predicts multiple sclerosis

Abstract

Objective We previously showed that serum IgG repertoires distinguished multiple sclerosis (MS) patients from healthy subjects and from patients with other inflammatory neurological diseases (OIND). We questioned whether the serum IgG repertoire of patients presenting a clinically isolated syndrome (CIS) could predict MS. Methods The global IgG immune responses against brain antigens in sera from 50 CIS patients were evaluated by immunoblotting. The IgG reactivities were compared with those from MS sera (n = 82), healthy sera (n = 27), and sera from OIND (n = 42). A linear discriminant analysis (LDA) defined a score for each individual. Results About 78% of scores obtained from CIS patients were located in the “MS area.” During the follow-up (3.5 ± 1.3 years), 28 patients fulfilled the McDonald criteria for MS, 15 patients remained CIS, and 7 patients developed OIND. Among the patients with an LDA score in the “MS area,” 61.5% converted to MS. Discussion Our results suggest that a pathological distortion of the self-reactive IgG repertoire occurs early so that immunomodulating treatment should be started as early as possible; they also highlight the early involvement of B cells in the physiopathological process in MS.