Evolution of antiplatelet antibodies after H pylori infection. Platelets may be activated by binding of first-generation H pylori antibodies (1) to platelet FcγRIIA or through an interaction between H pylori–bound von Willebrand factor (VWF) and platelet glycoprotein IB (gpIB). Activation may promote platelet clearance and antigen presentation, which augments production of antibacterial antibodies. Somatic mutation may lead to the development of second-generation antibodies (2) that either recognize bacterially derived factors that bind to platelets (3) or crossreact with platelet antigens (4). Improved mucosal permeability or bacterial eradication with proton-pump inhibitors and antibiotics may initiate the clinical response in patients with anti–H pylori antibodies (early response), which may be followed by a decrease in bacterial antigen and reduction in the titer of crossreacting antibody (late durable response). In patients with protracted disease unresponsive to antibiotic eradication, antibodies to H pylori may have undergone additional somatic mutations (third-generation antibodies; [5]) that lose their reactivity with the inciting antigen, but retain platelet reactivity (6) leading to early relapse or no response. APC indicates antigen-presenting cell. Professional illustration by Kenneth Xavier Probst.