A Mechanism of Cell Destruction in Individuals Sensitized to Foreign Antigens and Its Implications in Auto-immunity

NIH Conference1 March 1964A Mechanism of Cell Destruction in Individuals Sensitized to Foreign Antigens and Its Implications in Auto-immunityCombined Clinical Staff Conference at the National Institutes of HealthN. RAPHAEL SHULMAN, M.D.N. RAPHAEL SHULMAN, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-3-506 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDrug purpura (1-6), drug hemolytic anemia (7-9), and drug leukopenia (10-12) are now classic examples of diseases in which sensitization to a foreign antigen causes destruction of the sensitized individual's own cells. In these disorders, it is known (1, 2) that the drug somehow elicits antibody, and that the presence of drug is required for antibody to attach to the specific cells that are destroyed. However, the question ofhowantibodies against drug antigens become attached to autologous cells, the related questions of how a drug stimulates antibody, and why a particular cell type is affected have been matters of...References1. ACKROYD JF: The pathogenesis of thrombocytopenic purpura due to hypersensitivity to sedormid. Clin. Sci. 7: 249, 1949. MedlineGoogle Scholar2. ACKROYD JF: Role of complement in sedormid purpura. Clin. Sci. 10: 185, 1951. MedlineGoogle Scholar3. BOLTONDAMESHEK FGW: Thrombocytopenic purpura due to quinidine. Blood 11: 527, 1956. CrossrefMedlineGoogle Scholar4. SHULMAN NR: Immunoreactions involving platelets. I. A steric and kinetic model for formation of a complex from a human antibody, quinidine as a haptene, and platelets; and for fixation of complement by the complex. J. Exp. Med. 107: 665, 1958. CrossrefMedlineGoogle Scholar5. SHULMAN NR: Immunoreactions involving platelets. IV. Studies on the pathogenesis of thrombocytopenia in drug purpura using test doses of quinidine in sensitized individuals; their implications in idiopathic thrombocytopenic purpura. Ibid, p. 711. Google Scholar6. ACKROYD JF: The immunological basis of purpura due to drug hypersensitivity. Proc. Roy. Soc. Med. 55: 30, 1962. CrossrefMedlineGoogle Scholar7. HARRIS JW: Studies on the mechanism of a drug-induced hemolytic anemia. J. Lab. Clin. Med. 47: 760, 1956. MedlineGoogle Scholar8. FREEDMANBARRBRODY ALPSEA: Hemolytic anemia due to quinidine: observations on its mechanism. Amer. J. Med. 20: 806, 1956. CrossrefMedlineGoogle Scholar9. MACGIBBONLOUGHRIDGEHOURIHANEBOYD BHLWDODW: Autoimmune haemolytic anaemia with acute renal failure due to phenacetin and p-aminosalicylic acid. Lancet I: 7, 1960. CrossrefGoogle Scholar10. MOESCHLINWAGNER SK: Leukocytenagglutinine als ursache von agranulocytosen (Pyramidon usw). Schweiz. Med. Wschr. 82: 1104, 1952. MedlineGoogle Scholar11. OFSTADLUND-JOHANSEN JP: Trombocytopeni, granulocytopeni og positiv direkte Coombs' reaksjon forårsaket av kinidin. Nord. Med. 63: 606, 1960. MedlineGoogle Scholar12. DAUSSETBERGEROT-BLONDEL JY: Étude d'un anticorps allergique actif en présence de para-amino-salicylate de soude (PAS) contre les hématies, les leucocytes et les plaquettes humaines. Vox Sang. 6: 91, 1961. CrossrefMedlineGoogle Scholar13. SHULMANASTERLEITNERHILLER NRRHAMC: Immunoreactions involving platelets. V. Post-transfusion purpura due to a complement-fixing antibody against a genetically controlled platelet antigen. A proposed mechanism for thrombocytopenia and its relevance in "autoimmunity." J. Clin. Invest. 40: 1597, 1961. CrossrefMedlineGoogle Scholar14. SHULMAN NR: Immunoreactions involving platelets. III. Quantitative aspects of platelet agglutination, inhibition of clot retraction, and other reactions caused by the antibody of quinidine purpura. J. Exp. Med. 107: 697, 1958. CrossrefMedlineGoogle Scholar15. SHULMAN NR: Mechanism of blood cell damage by adsorption of antigen-antibody complexes, in Third International Symposium on Immunopathology, edited by GRABAR, P., and MIESCHER, P., B. Schwabe & Company, Basel, 1963, pp. 338-352. Google Scholar16. KAHNBROD HRRC: Thrombocytopenia due to stibophen (1 case). Arch. Intern. Med. (Chicago) 108: 496, 1961. CrossrefMedlineGoogle Scholar17. LANDSTEINER K: The Specificity of Serological Reactions, Harvard University Press, Cambridge, 1946, p. 156. Google Scholar18. LANNICAMPBELL FDH: A search for heterologating antibody and the significance of the results to the mechanism of antibody formation. Stanford Med. Bull. 6: 97, 1948. MedlineGoogle Scholar19. EISENCARSTENBELMAN HNMES: Studies of hypersensitivity to low molecular weight substances. III. The 2, 4-dinitrophenol group as a determinant in the precipitin reaction. J. Immun. 73: 296, 1954. MedlineGoogle Scholar20. NETER E: Bacterial hemagglutination and hemolysis. Bact. Rev. 20: 166, 1956. CrossrefMedlineGoogle Scholar21. LAMANNA C: Adhesion of foreign particles to particulate antigens in the presence of antibody and complement (serological adhesion). Bact. Rev. 21: 30, 1957. CrossrefMedlineGoogle Scholar22. NELSONNELSON DSRA: On the mechanism of immune-adherence. II. Analogy to mixed aggregation of sensitized antigens in the presence of complement. Yale J. Biol. Med. 31: 201, 1959. MedlineGoogle Scholar23. BOYDENANDERSEN SVME: Agglutination of normal erythrocytes in mixtures of antibody and antigen, and haemolysis in the presence of complement. Brit. J. Exp. Path. 36: 162, 1955. MedlineGoogle Scholar24. MIESCHERCOOPER PN: The fixation of soluble antigen-antibody complexes upon thrombocytes. Vox Sang. 5: 138, 1960. Google Scholar25. ALEXANDERWRIGHTBALDWIN MMGGAC: Observations on the agglutination of polysaccharide-treated erythrocytes by tularemia antisera. J. Exp. Med. 91: 561, 1950. CrossrefMedlineGoogle Scholar26. ZUCKERLEYBORRELLIMAYERFIRMAT MBABJKJ: Thrombocytopenia with a circulating platelet agglutinin, platelet lysin and clot retraction inhibitor. Blood 14: 148, 1959. CrossrefMedlineGoogle Scholar27. VAN LOGHEMDORFMEIJERVAN DER HART JJHM: Serological and genetical studies on a platelet antigen (Zw). Vox Sang. 4: 161, 1959. CrossrefMedlineGoogle Scholar28. MAYER M: Unpublished information presented at a Complement Workshop, National Institutes of Health, February, 1963. Google Scholar29. MÜLLER-EBERHARD HJ: Chemical aspects of human complement compounds, in Mechanism of Cell and Tissue Damage Produced by Immune Reactions. IInd International Symposium on Immunopathology, edited by GRABAR, P., and MIESCHER, P., B. Schwabe & Company, Basel, 1962, p. 23. Google Scholar30. HARRINGTONMINNICHARIMURA WJVG: The autoimmune thrombocytopenias, in Progress in Hematology, Vol. I, edited by TOCANTINS, L. M., Grune & Stratton, New York, 1956, p. 166. Google Scholar31. CORNUPSHAW MJD: Evaluation of platelet antibodies in idiopathic thrombocytopenic purpura. Arch Intern. Med (Chicago) 109: 157, 1962. CrossrefGoogle Scholar32. JACKSONSCHMIDZIEVELEVINCONLEY DPHJPDJCL: Nature of a platelet-agglutinating factor in serum of patients with idiopathic thrombocytopenic purpura. J. Clin. Invest. 42: 383, 1963. CrossrefMedlineGoogle Scholar33. SHULMANMARDERALEDORTHILLER NRVJLMMC: Complement-fixing isoantibodies against antigens common to platelets and leukocytes. Trans. Ass. Amer. Physicians 75: 89, 1962. MedlineGoogle Scholar34. SWISHER SN: Studies of the mechanisms of erythrocyte destruction initiated by antibodies. Trans. Ass. Amer. Physicians 67: 124, 1954. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, MarylandThis is an edited transcription of a combined clinical staff conference at the Clinical Center, Bethesda, Maryland, by the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, United States Public Health Service, Department of Health, Education, and Welfare.Part of this material was presented at the April 30, 1963 meeting of the Association of American Physicians, and appears in the Trans. Ass. Amer. Physicians 76: 72, 1963.Requests for reprints should be addressed to N. Raphael Shulman, M.D., National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland 20014. 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PHYSIOLOGIC, SEROLOGIC AND ISOTOPIC STUDIESSplenectomy 1 March 1964Volume 60, Issue 3Page: 506-521KeywordsAntigensArthritisDrugsGeneticsHemolytic anemiaMedical servicesMetabolic disordersNeutrophilsPrevention, policy, and public health Issue Published: 1 March 1964 PDF DownloadLoading ...