Abstract
The study of antibodies against Interferon-β (IFN-β) in treated multiple sclerosis (MS) patients has focused primarily on detection and quantification, with no single method of detection providing a comprehensive characterization. We assessed serial samples of 18 MS patients, treated with IFN-β for between 66 and 198 months, to characterize the affinity maturation of these antibodies using a biosensor-based approach (Biacore™). Biacore utilizes the principles of surface plasmon resonance (SPR) with data from the dissociation phase of the antigen–antibody reaction being inversely proportional to relative antibody affinity. In patients with neutralizing antibodies (NAbs+), mean antibody dissociation rates decreased from 0.00118 ± 0.00030 s−1 at month 6 to 0.00021 ± 0.00008 s−1 at month 36, followed by a slight increase to 0.00027 ± 0.00003 s−1 at month 60. In NAb− patients, mean antibody dissociation rates decreased only very slightly from 0.00130 ± 0.00025 s−1 to 0.00105 ± 0.00020 s−1 at month 18, followed by a gradual increase to 0.00243 ± 0.00099 s−1 at month 60. Our study shows little improvement in antibody affinity in NAb− patients, in contrast to a marked increase in antibody affinity over time in NAb+ patients with a significant correlation between NAb titers and relative antibody dissociation rates (Spearman’s correlation, R2 = −0.374, p < 0.001). The evaluation of relative antibody affinities will contribute to a thorough understanding of the anti-IFN-β antibody response.
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