Herbert Eradat.

Richard R. Furman, M here .D., Jeff P. Sharman, M.D., Steven E. Coutre, M.D., Bruce D. Cheson, M.D., John M. Pagel, M.D., Ph.D., Peter Hillmen, M.B., Ch.B., Ph.D., Jacqueline C. Barrientos, M.D., Andrew D. Zelenetz, M.D., Ph.D., Thomas J. Kipps, M.D., Ph.D., Ian Flinn, M.D., Ph.D., Paolo Ghia, M.D., Ph.D., Herbert Eradat, M.D., Thomas Ervin, M.D., Nicole Lamanna, M.D., Bertrand Coiffier, M.D., Ph.D., Andrew R. Pettitt, Ph.D., F.R.C.Route., Shuo Ma, M.D., Ph.D., Stephan Stilgenbauer, M.D., Paula Cramer, M.D., Maria Aiello, M.A., Dave M. Johnson, B.S., Langdon L.

Collectively, these data provide support for the hypothesis that the functional capacity of the mutant C5, using its inability to bind to eculizumab together, account for the indegent response in individuals who bring this mutation. A new variant, c.Arg885Cys, was independently identified in an Argentinian individual of Asian ancestry, suggesting the need for this site in C5 acknowledgement by eculizumab and the racial and ethnic elements associated with this phenomenon. The Arg885His/Cys mutations are proximal to the C5 MG7 domain, close to the known epitope for binding of eculizumab21 and within the contact region between the C5 convertase and bound C5 substrate, as inferred by Laursen et al.22 Evidently, these mutations, in keeping with the high specificity of monoclonal antibody binding, disrupt the eculizumab epitope but keep up with the capability of C5m to undergo cleavage by the C5 convertase.