Supplementum 239: Annual Congress of the Swiss Society for Allergology and Immunology, jointly organised with the Viral Immunity Symposium

2019 Swiss Medical Weekly  
Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS), but in about 9% of the cases neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation. To understand the basis of the ADA response and the mechanism of ADA-mediated neutralization, we performed an in-depth analysis of the B and T cell response in two patients. By characterizing a large panel of NZM-specific monoclonal
more » ... antibodies, we found that, in both patients, the response was polyclonal and targeted different epitopes of the NZM variable region. The neutralizing activity was acquired through somatic mutations and correlated with a slow dissociation rate, a finding that was supported by structural data. Interestingly, in both patients, the analysis of the CD4+ T cell response, combined with mass spectrometry-based peptidomics, revealed a single immunodominant T cell epitope in the NZM variable region. Collectively, our study identifies the basis of T-B collaboration that drives neutralizing anti-idiotypic antibodies to NZM.
doi:10.4414/smw.2019.20441 fatcat:m4xmjyglfnea7hsy3sh2z52224