Adalimumab elicits a restricted anti-idiotypic antibody response in autoimmune patients resulting in functional neutralisation

Abstract

The humoral immune response against adalimumab is highly restricted and limited to the idiotype of the therapeutic antibody. All antibodies result in functional neutralisation of the drug, thereby providing a mechanism by which AAA formation leads to clinical non-response.

Functional Analysis of the Anti-adalimumab Response Using Patient-derived Monoclonal Antibodies

“…Furthermore, it demonstrates that larger immune complexes may still be formed if anti-adalimumab antibodies develop. These findings complement a previous study where only small immune complexes could be detected in the sera of patients treated with adalimumab (8), and the findings suggest that if larger immune complexes are formed in vivo, they will probably be rapidly cleared.…”

“…Isolation, Proliferation, and Identification of Adalimumabspecific Single B-cells-Antigen-specific B-cells were isolated and cultured as described before (8). In short, PBMC's were isolated using a Percoll gradient, and B-cells were isolated using anti-CD19 beads.…”

“…Cells were cultured in the presence of CD40 ligand-expressing cells and a cytokine mixture. After 10 -14 days, the supernatants were tested for the presence of ADA using the bridging ELISA as described before (8). Furthermore, the isotype of each clone was determined by ELISA.…”

“…All incubations were performed in high performance ELISA buffer (Sanquin). Binding of biotinylated antibody was detected using streptavidin-poly-HRP as described before (8).…”

“…Second, the formation of neutralizing antibodies can prevent the therapeutic agent from binding to its target. In the case of adalimumab, a fully human anti-TNF agent, recent data indicate that essentially all ADA are anti-idiotypic antibodies, directed against the TNF binding region of adalimumab and resulting in neutralization of the drug (8). This is confirmed by inhibition experiments showing that TNF completely prevents binding of ADA in patient sera (9).…”