In vitro production of antibodies to histones in patients receiving chronic procainamide therapy

Objective. Procainamide related autoimmunity is characterized by the produc tion of antibodies to histories and, in particular, to the H2A-2B dimer. We evaluated in vitro production of antibodies to total histones and the H2A- 2B dimer by peripheral blood mononuclear cells (PBMC) from patients chronic ally exposed to procainamide and related this to in vivo production, and as sessed possible immunostimulatory response by the postulated reactive metab olite procainamide hydroxylamine (PAHA) using PAHA conjugated autologous er ythrocytes. Methods. We evaluated in vitro spontaneous and mitogen induced production o f histone antibodies by PBMC from 26 asymptomatic patients, who were chroni cally receiving procainamide, in the presence and absence of PAHA conjugate d autologous erythrocytes. Correlations with in vivo production were sought . Results. PBMC from 9 patients revealed significant spontaneous production o f histone antibodies, of whom 2 developed procainamide related lupus within 2 mo of the evaluation. There was a significant increase in in vitro produ ction of antibodies to total histories by PBMC that had been cultured in th e presence of PAHA-autologous erythrocyte conjugates, but in the absence of mitogens, from 15 (65%) of 23 patients, and of antibodies to H2A-2B by cel ls from 10 (42%) of 24 patients. Patients' cells that were co-cultured with PAHA-erythrocyte conjugates produced significantly greater amounts of anti bodies to both total histories (p=0.03) and the H2A-2B dimer (p=0.009) comp ared with those cultured alone. Co-culture with similarly pretreated erythr ocytes also resulted in a significant increase in the production of antibod ies to total histories (p<0.001). but not to the H2A-H2B dimer, by cells fr om controls. Conclusion. Some patients receiving chronic procainamide therapy have spont aneous production of histone antibodies. Co-culture with PAHA-erythrocyte c onjugates resulted in significantly greater production. suggesting an immun omodulating effect by this metabolite.