Abstract
The specificity of the in vivo humoral immune response elicited by procainamide was examined by solid-phase assays, immunofluorescence, immunoprecipitation and a cytotoxicity assay. Serial samples obtained from patients during their procainamide therapy showed a progressive increase in antibodies to histones and denatured DNA, and both activities decreased after discontinuation of therapy. In contrast antibodies to tetanus, human IgG (rheumatoid factor) and heterologous lymphocytes were unaffected by procainamide treatment, indicating that they were not drug-induced. Of 29 sera examined by protein-A-facilitated immunoprecipitation, four sera had antibody to ribosomal RNA and three sera immunoprecipitated a 40kD protein. Antinuclear antibodies were invariably present but absorption studies showed that these activities were due to anti-histone antibodies. These results indicate that procainamide-induced autoimmunity is characterized predominantly by an anti-histone and anti-denatured DNA immune response.
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Selected References
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- Blomgren S. E., Condemi J. J., Vaughan J. H. Procainamide-induced lupus erythematosus. Clinical and laboratory observations. Am J Med. 1972 Mar;52(3):338–348. doi: 10.1016/0002-9343(72)90021-6. [DOI] [PubMed] [Google Scholar]
- Blomgren S. E. Drug-induced lupus erythematosus. Semin Hematol. 1973 Oct;10(4):345–349. [PubMed] [Google Scholar]
- Bluestein H. G., Zvaifler N. J., Weisman M. H., Shapiro R. F. Lymphocyte alteration by procainamide: relation to drug-induced lupus erythematosus syndrome. Lancet. 1979 Oct 20;2(8147):816–819. doi: 10.1016/s0140-6736(79)92174-3. [DOI] [PubMed] [Google Scholar]
- Francoeur A. M., Mathews M. B. Interaction between VA RNA and the lupus antigen La: formation of a ribonucleoprotein particle in vitro. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6772–6776. doi: 10.1073/pnas.79.22.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fritzler M. J., Tan E. M. Antibodies to histones in drug-induced and idiopathic lupus erythematosus. J Clin Invest. 1978 Sep;62(3):560–567. doi: 10.1172/JCI109161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodwin J. S., Searles R. P., Tung K. S. Immunological responses of healthy elderly population. Clin Exp Immunol. 1982 May;48(2):403–410. [PMC free article] [PubMed] [Google Scholar]
- Grossman L., Barland P. Histone reactivity of drug-induced antinuclear antibodies. A comparison of symptomatic and asymptomatic patients. Arthritis Rheum. 1981 Jul;24(7):927–931. doi: 10.1002/art.1780240710. [DOI] [PubMed] [Google Scholar]
- Hallgren H. M., Buckley C. E., 3rd, Gilbertsen V. A., Yunis E. J. Lymphocyte phytohemagglutinin responsiveness, immunoglobulins and autoantibodies in aging humans. J Immunol. 1973 Oct;111(4):1101–1107. [PubMed] [Google Scholar]
- Klajman A., Camin-Belsky N., Kimchi A., Ben-Efraim S. Occurrence, immunoglobulin pattern and specificity of antinuclear antibodies in sera of procaine amide treated patients. Clin Exp Immunol. 1970 Nov;7(5):641–649. [PMC free article] [PubMed] [Google Scholar]
- Klajman A., Farkas R., Ben-Efraim S. Reactions of procaine amide-induced antinuclear antibodies with fractions derived from calf thymus nuclei. Int Arch Allergy Appl Immunol. 1972;43(4):630–638. doi: 10.1159/000230875. [DOI] [PubMed] [Google Scholar]
- Klajman A., Farkas R., Gold E., Ben-Efraim S. Procainamide-induced antibodies to nucleoprotein, denatured and native DNA in human subjects. Clin Immunol Immunopathol. 1975 Mar;3(4):525–530. doi: 10.1016/0090-1229(75)90077-x. [DOI] [PubMed] [Google Scholar]
- Klajman A., Kafri B., Shohat T., Drucker I., Moalem T., Jaretzky A. The prevalence of antibodies to histones induced by procainamide in old people, in cancer patients, and in rheumatoid-like disease. Clin Immunol Immunopathol. 1983 Apr;27(1):1–8. doi: 10.1016/0090-1229(83)90050-8. [DOI] [PubMed] [Google Scholar]
- Koffler D., Carr R. I., Agnello V., Fiezi T., Kunkel H. G. Antibodies to polynucleotides: distribution in human serums. Science. 1969 Dec 26;166(3913):1648–1649. doi: 10.1126/science.166.3913.1648. [DOI] [PubMed] [Google Scholar]
- Koffler D., Carr R., Agnello V., Thoburn R., Kunkel H. G. Antibodies to polynucleotides in human sera: antigenic specificity and relation to disease. J Exp Med. 1971 Jul 1;134(1):294–312. doi: 10.1084/jem.134.1.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lee S. L., CHase P. H. Drug-induced systemic lupus erythematosus: a critical review. Semin Arthritis Rheum. 1975 Aug;5(1):83–103. doi: 10.1016/0049-0172(75)90024-4. [DOI] [PubMed] [Google Scholar]
- Lerner M. R., Boyle J. A., Hardin J. A., Steitz J. A. Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science. 1981 Jan 23;211(4480):400–402. doi: 10.1126/science.6164096. [DOI] [PubMed] [Google Scholar]
- Matter L., Schopfer K., Wilhelm J. A., Nyffenegger T., Parisot R. F., De Robertis E. M. Molecular characterization of ribonucleoprotein antigens bound by antinuclear antibodies. A diagnostic evaluation. Arthritis Rheum. 1982 Nov;25(11):1278–1283. doi: 10.1002/art.1780251102. [DOI] [PubMed] [Google Scholar]
- McNeilage L. J., Whittingham S., Mackay I. R. Autoantibodies reactive with small ribonucleoprotein antigens: a convergence of molecular biology and clinical immunology. J Clin Lab Immunol. 1984 Sep;15(1):1–17. [PubMed] [Google Scholar]
- Miller K. B., Salem D. Immune regulatory abnormalities produced by procainamide. Am J Med. 1982 Oct;73(4):487–492. doi: 10.1016/0002-9343(82)90326-6. [DOI] [PubMed] [Google Scholar]
- Molina J., Dubois E. L., Bilitch M., Bland S. L., Friou G. J. Procainamide-induced serologic changes in asymptomatic patients. Arthritis Rheum. 1969 Dec;12(6):608–614. doi: 10.1002/art.1780120608. [DOI] [PubMed] [Google Scholar]
- Ochi T., Goldings E. A., Lipsky P. E., Ziff M. Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro. J Clin Invest. 1983 Jan;71(1):36–45. doi: 10.1172/JCI110749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Portanova J. P., Rubin R. L., Joslin F. G., Agnello V. D., Tan E. M. Reactivity of anti-histone antibodies induced by procainamide and hydralazine. Clin Immunol Immunopathol. 1982 Oct;25(1):67–79. doi: 10.1016/0090-1229(82)90166-0. [DOI] [PubMed] [Google Scholar]
- Rubin R. L., Joslin F. G., Tan E. M. An improved ELISA for anti-native DNA by elimination of interference by anti-histone antibodies. J Immunol Methods. 1983 Oct 28;63(3):359–366. doi: 10.1016/s0022-1759(83)80009-x. [DOI] [PubMed] [Google Scholar]
- Rubin R. L., McNally E. M., Nusinow S. R., Robinson C. A., Tan E. M. IgG antibodies to the histone complex H2A-H2B characterize procainamide-induced lupus. Clin Immunol Immunopathol. 1985 Jul;36(1):49–59. doi: 10.1016/0090-1229(85)90038-8. [DOI] [PubMed] [Google Scholar]
- Rubin R. L., Moudrianakis E. N. The F3-F2a1 complex as a unit in the self-assembly of nucleoproteins. Biochemistry. 1975 Apr 22;14(8):1718–1726. doi: 10.1021/bi00679a026. [DOI] [PubMed] [Google Scholar]
- Searles R. P., Okudaira K., Savage S. M., Goodwin J. S. Ia specific antilymphocyte antibodies in rheumatoid arthritis. Arthritis Rheum. 1983 Apr;26(4):486–493. doi: 10.1002/art.1780260406. [DOI] [PubMed] [Google Scholar]
- Terasaki P. I., Mottironi V. D., Barnett E. V. Cytotoxins in disease. Autocytotoxins in lupus. N Engl J Med. 1970 Oct 1;283(14):724–728. doi: 10.1056/NEJM197010012831403. [DOI] [PubMed] [Google Scholar]
- Whittingham S., Mackay I. R., Whitworth J. A., Sloman G. Antinuclear antibody response to procainamide in man and laboratory animals. Am Heart J. 1972 Aug;84(2):228–234. doi: 10.1016/0002-8703(72)90337-7. [DOI] [PubMed] [Google Scholar]
- Winfield J. B., Koffler D., Kunkel H. G. Development of antibodies to ribonucleoprotein following short-term therapy with procainamide. Arthritis Rheum. 1975 Nov-Dec;18(6):531–534. doi: 10.1002/art.1780180601. [DOI] [PubMed] [Google Scholar]
- Woosley R. L., Drayer D. E., Reidenberg M. M., Nies A. S., Carr K., Oates J. A. Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. N Engl J Med. 1978 May 25;298(21):1157–1159. doi: 10.1056/NEJM197805252982101. [DOI] [PubMed] [Google Scholar]