Mechanism for immune-mediated drug-induced thrombotic microangiopathy (DITMA) and other systemic reactions caused by quinine

(A) Naturally occurring antibodies that react very weakly with antigens on autologous cells* may be present in certain individuals.
(B) Drugs can bind to the complementarity-determining regions (CDR) of the naturally occurring antibodies, remodeling their structure and increasing their binding affinity to the antigenic epitopes by >10,000-fold. The physiologic response to antigen-antibody binding provokes cell injury and TMA. These antibodies persist for years; subsequent drug exposure can cause an immediate reaction.