The chemical and immunoglobulin structural features necessary for reactions of quinine‐dependent antibodies to neutrophils

Abstract

Previously described were three patients with quinine-dependent antibodies to neutrophils, platelets, and red cells who had episodic pancytopenia and renal failure. The nature of the antibody-drug-neutrophil interactions was investigated with sera from these patients. Sera from all three patients were tested against neutrophils in flow cytometry in the presence of several compounds related to quinine. IgG and Fab and F(ab')2 fragments were prepared from the serum of one patient and tested against neutrophils in flow cytometry and immunoprecipitation in the presence of quinine and related compounds. In flow cytometry, sera from all three patients plus quinidine reacted with neutrophils. Sera from Patients 1 and 3 reacted with neutrophils in the presence of cinchonidine (desmethoxy-quinine) and serum from Patient 3 also reacted with neutrophils in the presence of cinchonine (desmethoxy-quinidine). None of the sera reacted with neutrophils in the presence of chloroquine or primaquine. Serum from Patient 3 plus quinolinic acid, a tryptophan metabolite, reacted with neutrophils, but sera from the other two patients did not. Patient 3 serum plus tryptophan or another tryptophan metabolite, quinalidic acid, did not react with neutrophils. IgG from Patient 3 serum reacted with neutrophils in flow cytometry in the presence of quinine, quinidine, cinchonidine, cinchonine, and quinolinic acid. F(ab')2 fragments plus quinine or cinchonidine also reacted with neutrophils, but Fab fragments plus quinine did not. In the presence of quinine, Patient 3 IgG immunoprecipitated the 85- and 60-kDa molecules and F(ab')2 fragments immunoprecipitated the 85-kDa molecule. Patient 3 serum plus quinidine, cinchonidine, cinchonine, and quinolinic acid immunoprecipitated the 130- and 85-kDa molecules, but not the 60-kDa molecule. Quinine-dependent neutrophil antibodies often react with neutrophils in the presence of quinidine and related compounds. These reactions were mediated by the F(ab')2 domain of IgG.