{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:43:27Z","timestamp":1781304207676,"version":"3.54.1"},"reference-count":42,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5186","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1994,11,4]]},"abstract":"<jats:p>Drug-induced lupus is a serious side effect of certain medications, but the chemical features that confer this property and the underlying pathogenesis are puzzling. Prototypes of all six therapeutic classes of lupus-inducing drugs were highly cytotoxic only in the presence of activated neutrophils. Removal of extracellular hydrogen peroxide before, but not after, exposure of the drug to activated neutrophils prevented cytotoxicity. Neutrophil-dependent cytotoxicity required the enzymatic action of myeloperoxidase, resulting in the chemical transformation of the drug to a reactive product. The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo.<\/jats:p>","DOI":"10.1126\/science.7973636","type":"journal-article","created":{"date-parts":[[2006,10,6]],"date-time":"2006-10-06T00:01:25Z","timestamp":1160092885000},"page":"810-813","source":"Crossref","is-referenced-by-count":179,"title":["Transformation of Lupus-Inducing Drugs to Cytotoxic Products by Activated Neutrophils"],"prefix":"10.1126","volume":"266","author":[{"given":"Xiaoxia","family":"Jiang","sequence":"first","affiliation":[{"name":"W. M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gus","family":"Khursigara","sequence":"additional","affiliation":[{"name":"W. M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Rubin","sequence":"additional","affiliation":[{"name":"W. M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","unstructured":"United States Pharmacopeia Dispensing Information 14 1 : 417 (1994)."},{"key":"e_1_2_1_2_1","first-page":"482","volume":"113","year":"1989","unstructured":"ADAMS, L.E., IMMUNOMODULATORY EFFECTS OF PROCAINAMIDE METABOLITES - THEIR IMPLICATIONS IN DRUG-RELATED LUPUS, JOURNAL OF LABORATORY AND CLINICAL MEDICINE 113: 482 (1989).","journal-title":"JOURNAL OF LABORATORY AND CLINICAL MEDICINE"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1177\/096120339300200205","volume":"2","year":"1993","unstructured":"ADAMS, L.E., GENETIC, IMMUNOLOGICAL AND BIOTRANSFORMATION STUDIES OF PATIENTS ON PROCAINAMIDE, LUPUS 2: 89 (1993).","journal-title":"LUPUS"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/175859a0","volume":"175","year":"1955","unstructured":"ANDREAE, W.A., SENSITIVE METHOD FOR THE ESTIMATION OF HYDROGEN PEROXIDE IN BIOLOGICAL MATERIALS, NATURE 175: 859 (1955).","journal-title":"NATURE"},{"key":"e_1_2_1_5_1","first-page":"13","volume":"234","year":"1985","unstructured":"AUCOIN, D.P., PROPYLTHIOURACIL-INDUCED IMMUNE-MEDIATED DISEASE IN THE CAT, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 234: 13 (1985).","journal-title":"JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1056\/NEJM197803232981205","volume":"298","year":"1978","unstructured":"BABIOR, B.M., OXYGEN-DEPENDENT MICROBIAL KILLING BY PHAGOCYTES .1., NEW ENGLAND JOURNAL OF MEDICINE 298: 659 (1978).","journal-title":"NEW ENGLAND JOURNAL OF MEDICINE"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1006\/abbi.1993.1298","volume":"303","year":"1993","unstructured":"BARR, D.P., ON THE MECHANISM OF PEROXIDASE-CATALYZED OXYGEN PRODUCTION, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 303: 377 (1993).","journal-title":"ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS"},{"key":"e_1_2_1_8_1","first-page":"345","volume":"10","year":"1973","unstructured":"BLOMGREN, S.E., DRUG-INDUCED LUPUS-ERYTHEMATOSUS, SEMINARS IN HEMATOLOGY 10: 345 (1973).","journal-title":"SEMINARS IN HEMATOLOGY"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1083\/jcb.63.1.251","volume":"63","year":"1974","unstructured":"BRETZ, U, BIOCHEMICAL AND MORPHOLOGICAL CHARACTERIZATION OF AZUROPHIL AND SPECIFIC GRANULES OF HUMAN NEUTROPHILIC POLYMORPHONUCLEAR LEUKOCYTES, JOURNAL OF CELL BIOLOGY 63: 251 (1974).","journal-title":"JOURNAL OF CELL BIOLOGY"},{"key":"e_1_2_1_10_1","first-page":"37","volume":"15","year":"1987","unstructured":"BUDINSKY, R.A., THE FORMATION OF PROCAINAMIDE HYDROXYLAMINE BY RAT AND HUMAN-LIVER MICROSOMES, DRUG METABOLISM AND DISPOSITION 15: 37 (1987).","journal-title":"DRUG METABOLISM AND DISPOSITION"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/rheumatology\/33.2.109","volume":"33","year":"1994","unstructured":"CAMBRIDGE, G, AUTOANTIBODIES TO MYELOPEROXIDASE IN IDIOPATHIC AND DRUG-INDUCED SYSTEMIC LUPUS-ERYTHEMATOSUS AND VASCULITIS, BRITISH JOURNAL OF RHEUMATOLOGY 33: 109 (1994).","journal-title":"BRITISH JOURNAL OF RHEUMATOLOGY"},{"key":"e_1_2_1_12_1","first-page":"107","volume":"5","year":"1983","unstructured":"CLARK, R.A., ADV INFLAMMAT RES 5: 107 (1983).","journal-title":"ADV INFLAMMAT RES"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","unstructured":"Dixon M. Enzymes 3 345 (1979).","DOI":"10.1016\/0378-3782(79)90046-X"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/0076-6879(90)86153-M","volume":"186","year":"1990","unstructured":"EASTMOND, D.A., XENOBIOTIC ACTIVATION BY STIMULATED HUMAN POLYMORPHONUCLEAR LEUKOCYTES AND MYELOPEROXIDASE, METHODS IN ENZYMOLOGY 186: 579 (1990).","journal-title":"METHODS IN ENZYMOLOGY"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0307-742X(21)00203-4","volume":"8","year":"1982","unstructured":"HARMON, C.E., DRUG-INDUCED LUPUS - CLINICAL AND SEROLOGICAL STUDIES, CLINICS IN RHEUMATIC DISEASES 8: 121 (1982).","journal-title":"CLINICS IN RHEUMATIC DISEASES"},{"key":"e_1_2_1_16_1","first-page":"239","year":"1989","unstructured":"Hein, D. W., Autoimmunity and Toxicology: 239 (1989).","journal-title":"Autoimmunity and Toxicology"},{"key":"e_1_2_1_17_1","first-page":"205","volume":"20","year":"1992","unstructured":"HOFSTRA, A.H., METABOLISM OF ISONIAZID BY ACTIVATED LEUKOCYTES - POSSIBLE ROLE IN DRUG-INDUCED LUPUS, DRUG METABOLISM AND DISPOSITION 20: 205 (1992).","journal-title":"DRUG METABOLISM AND DISPOSITION"},{"key":"e_1_2_1_18_1","first-page":"1673","volume":"18","year":"1991","unstructured":"HOFSTRA, A. H., JOURNAL OF RHEUMATOLOGY 18: 1673 (1991).","journal-title":"JOURNAL OF RHEUMATOLOGY"},{"key":"e_1_2_1_19_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3109\/10409238909082555","volume":"24","year":"1989","unstructured":"HURST, J.K., LEUKOCYTIC OXYGEN ACTIVATION AND MICROBICIDAL OXIDATIVE TOXINS, CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY 24: 271 (1989).","journal-title":"CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY"},{"key":"e_1_2_1_20_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0009-2797(91)90049-D","volume":"79","year":"1991","unstructured":"KELDER, P. P., CHEMICO-BIOLOGICAL INTERACTIONS 79: 15 (1991).","journal-title":"CHEMICO-BIOLOGICAL INTERACTIONS"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1006\/taap.1993.1175","volume":"122","year":"1993","unstructured":"KUBICKAMURANYI, M, T-LYMPHOCYTES IGNORE PROCAINAMIDE, BUT RESPOND TO ITS REACTIVE METABOLITES IN PERITONEAL-CELLS - DEMONSTRATION BY THE ADOPTIVE TRANSFER POPLITEAL LYMPH-NODE ASSAY, TOXICOLOGY AND APPLIED PHARMACOLOGY 122: 88 (1993).","journal-title":"TOXICOLOGY AND APPLIED PHARMACOLOGY"},{"key":"e_1_2_1_22_1","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1056\/NEJM197912203012506","volume":"301","year":"1979","unstructured":"LAHITA, R, ANTIBODIES TO NUCLEAR ANTIGENS IN PATIENTS TREATED WITH PROCAINAMIDE OR ACETYLPROCAINAMIDE, NEW ENGLAND JOURNAL OF MEDICINE 301: 1382 (1979).","journal-title":"NEW ENGLAND JOURNAL OF MEDICINE"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.4049\/jimmunol.152.3.1064","volume":"152","year":"1994","unstructured":"NAKASHIMA, I, REDOX MECHANISM AS ALTERNATIVE TO LIGAND-BINDING FOR RECEPTOR ACTIVATION DELIVERING DISREGULATED CELLULAR SIGNALS, JOURNAL OF IMMUNOLOGY 152: 1064 (1994).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_24_1","first-page":"380","volume":"81","year":"1990","unstructured":"NASSBERGER, L, AUTOANTIBODIES AGAINST NEUTROPHIL CYTOPLASM COMPONENTS IN SYSTEMIC LUPUS-ERYTHEMATOSUS AND IN HYDRALAZINE-INDUCED LUPUS, CLINICAL AND EXPERIMENTAL IMMUNOLOGY 81: 380 (1990).","journal-title":"CLINICAL AND EXPERIMENTAL IMMUNOLOGY"},{"key":"e_1_2_1_25_1","first-page":"195","volume":"20","year":"1981","unstructured":"NELSON, S.D., PEROXIDASE-MEDIATED FORMATION OF REACTIVE METABOLITES OF ACETAMINOPHEN, MOLECULAR PHARMACOLOGY 20: 195 (1981).","journal-title":"MOLECULAR PHARMACOLOGY"},{"key":"e_1_2_1_26_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0889-857X(21)00226-X","volume":"20","year":"1994","unstructured":"YUNG, R.L., DRUG-INDUCED LUPUS, RHEUMATIC DISEASE CLINICS OF NORTH AMERICA 20: 61 (1994).","journal-title":"RHEUMATIC DISEASE CLINICS OF NORTH AMERICA"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1172\/JCI114020","volume":"83","year":"1989","unstructured":"RUBIN, R.L., METABOLISM OF PROCAINAMIDE TO THE CYTO-TOXIC HYDROXYLAMINE BY NEUTROPHILS ACTIVATED INVITRO, JOURNAL OF CLINICAL INVESTIGATION 83: 1336 (1989).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_28_1","first-page":"833","volume":"242","year":"1987","unstructured":"RUBIN, R.L., CYTOTOXICITY OF OXIDATIVE METABOLITES OF PROCAINAMIDE, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 242: 833 (1987).","journal-title":"JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS"},{"key":"e_1_2_1_29_1","unstructured":"RUBIN R.L. unpublished data."},{"key":"e_1_2_1_30_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1128\/AAC.27.3.399","volume":"27","year":"1985","unstructured":"SHOEB, H.A., PEROXIDASE-MEDIATED OXIDATION OF ISONIAZID, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 27: 399 (1985).","journal-title":"ANTIMICROBIAL AGENTS AND CHEMOTHERAPY"},{"key":"e_1_2_1_31_1","first-page":"282","year":"1979","unstructured":"Smolen, J. E., Arthritis and Allied Conditions: 282 (1979).","journal-title":"Arthritis and Allied Conditions"},{"key":"e_1_2_1_32_1","first-page":"184","volume":"11","year":"1983","unstructured":"STREETER, A.J., STUDIES ON THE INVIVO METABOLISM OF HYDRALAZINE IN THE RAT, DRUG METABOLISM AND DISPOSITION 11: 184 (1983).","journal-title":"DRUG METABOLISM AND DISPOSITION"},{"key":"e_1_2_1_33_1","first-page":"77","volume":"12","year":"1984","unstructured":"UETRECHT, J.P., METABOLISM OF PROCAINAMIDE TO A HYDROXYLAMINE BY RAT AND HUMAN HEPATIC MICROSOMES, DRUG METABOLISM AND DISPOSITION 12: 77 (1984).","journal-title":"DRUG METABOLISM AND DISPOSITION"},{"key":"e_1_2_1_34_1","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1016\/0006-2952(89)90477-2","volume":"38","year":"1989","unstructured":"VANZYL, J.M., ISONIAZID-MEDIATED IRREVERSIBLE INHIBITION OF THE MYELOPEROXIDASE ANTIMICROBIAL SYSTEM OF THE HUMAN NEUTROPHIL AND THE EFFECT OF THYRONINES, BIOCHEMICAL PHARMACOLOGY 38: 2363 (1989).","journal-title":"BIOCHEMICAL PHARMACOLOGY"},{"key":"e_1_2_1_35_1","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/0006-2952(90)90478-4","volume":"40","year":"1990","unstructured":"VANZYL, J.M., ACTIVATION OF CHLORPROMAZINE BY THE MYELOPEROXIDASE SYSTEM OF THE HUMAN NEUTROPHIL, BIOCHEMICAL PHARMACOLOGY 40: 947 (1990).","journal-title":"BIOCHEMICAL PHARMACOLOGY"},{"key":"e_1_2_1_36_1","first-page":"354","volume":"19","year":"1991","unstructured":"WALDHAUSER, L, OXIDATION OF PROPYLTHIOURACIL TO REACTIVE METABOLITES BY ACTIVATED NEUTROPHILS - IMPLICATIONS FOR AGRANULOCYTOSIS, DRUG METABOLISM AND DISPOSITION 19: 354 (1991).","journal-title":"DRUG METABOLISM AND DISPOSITION"},{"key":"e_1_2_1_37_1","first-page":"1","volume":"4","year":"1980","unstructured":"WEINSTEIN, A, PROG CLIN IMMUNOL 4: 1 (1980).","journal-title":"PROG CLIN IMMUNOL"},{"key":"e_1_2_1_38_1","first-page":"691","volume":"19","year":"1991","unstructured":"WHEELER, J.F., DETERMINATION OF METABOLICALLY DERIVED NITROPROCAINAMIDE IN THE URINE OF PROCAINAMIDE-DOSED HUMANS AND RATS BY LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION, DRUG METABOLISM AND DISPOSITION 19: 691 (1991).","journal-title":"DRUG METABOLISM AND DISPOSITION"},{"key":"e_1_2_1_39_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1093\/oxfordjournals.bmb.a072387","volume":"46","year":"1990","unstructured":"WOODHOUSE, K.W., HEPATIC DRUG-METABOLISM AND AGING, BRITISH MEDICAL BULLETIN 46: 22 (1990).","journal-title":"BRITISH MEDICAL BULLETIN"},{"key":"e_1_2_1_40_1","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1056\/NEJM197805252982101","volume":"298","year":"1978","unstructured":"WOOSLEY, R.L., EFFECT OF ACETYLATOR PHENOTYPE ON RATE AT WHICH PROCAINAMIDE INDUCES ANTI-NUCLEAR ANTIBODIES AND LUPUS SYNDROME, NEW ENGLAND JOURNAL OF MEDICINE 298: 1157 (1978).","journal-title":"NEW ENGLAND JOURNAL OF MEDICINE"},{"key":"e_1_2_1_41_1","first-page":"254","year":"1988","unstructured":"Worthington, C. C., Worthington Enzyme Manual, Enzymes and Related Biochemicals: 254 (1988).","journal-title":"Worthington Enzyme Manual, Enzymes and Related Biochemicals"},{"key":"e_1_2_1_42_1","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0006-2952(91)90195-B","volume":"41","year":"1991","unstructured":"YAMAMOTO, K, FREE-RADICAL PRODUCTION AND SITE-SPECIFIC DNA DAMAGE INDUCED BY HYDRALAZINE IN THE PRESENCE OF METAL-IONS OR PEROXIDASE HYDROGEN-PEROXIDE, BIOCHEMICAL PHARMACOLOGY 41: 905 (1991).","journal-title":"BIOCHEMICAL PHARMACOLOGY"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.7973636","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T04:17:06Z","timestamp":1705292226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.7973636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,11,4]]},"references-count":42,"journal-issue":{"issue":"5186","published-print":{"date-parts":[[1994,11,4]]}},"alternative-id":["10.1126\/science.7973636"],"URL":"https:\/\/doi.org\/10.1126\/science.7973636","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,11,4]]}}}