STUDY OF PROCAINAMIDE HAPTEN-SPECIFIC ANTIBODIES IN RABBITS AND HUMANS

被引:10
作者
ADAMS, LE
ROBERTS, SM
DONOVANBRAND, R
ZIMMER, H
HESS, EV
机构
[1] UNIV CINCINNATI, MED CTR, DEPT MED, DIV IMMUNOL, CINCINNATI, OH 45267 USA
[2] UNIV CINCINNATI, DEPT CHEM, CINCINNATI, OH 45221 USA
[3] UNIV FLORIDA, CTR ENVIRONM & HUMAN TOXICOL, GAINESVILLE, FL 32611 USA
来源
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY | 1993年 / 15卷 / 08期
关键词
D O I
10.1016/0192-0561(93)90006-K
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Procainamide (PA) is the drug most commonly associated with the induction of autoantibodies and drug-related lupus (DRL). While the majority of these patients express autoantibodies, antibodies to the parent drug and metabolites, PA-hydroxylamine (PAHA) or nitroso-PA (NOPA), have not been reported in humans. Hapten-carrier conjugates were prepared using human hemoglobin (HgB) or autologous rabbit erythrocytes with PAHA or NOPA. PA was conjugated to rabbit serum albumin (RSA) or egg albumin (OVA) via diazotization and condensation methods. Rabbits were immunized with hapten conjugates in Freund's adjuvant. These hapten-carrier compounds (5 - 10 mug/ml) were used as test antigens for antibodies in sera from the rabbits and 40 patients on chronic PA treatment, 10 SLE patients, 33 elderly and 20 young normal controls by ELISA. Type I and II collagens were also used as test antigens for human sera. Sera from rabbits immunized with the PA compounds had elevated IgG antibody values to PA, PAHA and NOPA, but no autoantibodies. Absorption of the rabbit sera with the PA compounds reduced the antibody levels; ssDNA and histones failed to inhibit the total binding values. Mean binding to PA - OVA was 0.95 +/- 0.41 for PA patients and 1.37 +/- 0.26 standard error of means (S.E.M.) in the SLE patients compared to 0.37 +/- 0.14 S.E.M. in the normal sera (P less-than-or-equal-to 0.05); similar binding values to PAHA - HgB and NOPA - HgB were also observed. Sixty-eight percent of the PA patients had antibodies to type II collagen. Elevated binding values to PA compounds were inhibited by absorption of human sera with ssDNA or total histones; absorption with PA or PAHA had no significant effect. These findings suggest that sera from PA patients containing high titers of autoantibodies cross-react in vitro with unrelated antigens.
引用
收藏
页码:887 / 897
页数:11
相关论文
共 56 条
  • [1] EFFECTS OF PROCAINAMIDE HYDROXYLAMINE ON GENERATION OF REACTIVE OXYGEN SPECIES BY MACROPHAGES AND PRODUCTION OF CYTOKINES
    ADAMS, LE
    ROBERTS, SM
    CARTER, JM
    WHEELER, JF
    ZIMMER, HW
    DONOVANBRAND, RJ
    HESS, EV
    [J]. INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY, 1990, 12 (07): : 809 - 819
  • [2] DRUG-RELATED LUPUS - INCIDENCE, MECHANISMS AND CLINICAL IMPLICATIONS
    ADAMS, LE
    HESS, EV
    [J]. DRUG SAFETY, 1991, 6 (06) : 431 - 449
  • [3] ADAMS LE, 1989, J LAB CLIN MED, V113, P482
  • [4] GENETIC, IMMUNOLOGICAL AND BIOTRANSFORMATION STUDIES OF PATIENTS ON PROCAINAMIDE
    ADAMS, LE
    BALAKRISHNAN, K
    ROBERTS, SM
    BELCHER, R
    MONGEY, AB
    THOMAS, TJ
    HESS, EV
    [J]. LUPUS, 1993, 2 (02) : 89 - 98
  • [5] ADAMS LE, 1989, 7TH INT C IMM BERL
  • [6] ALARCONSEGOVIA D, 1969, MAYO CLIN PROC, V44, P664
  • [7] FILTER RADIOIMMUNOASSAY FOR ANTIBODIES TO REOVIRUS RNA IN SYSTEMIC LUPUS-ERYTHEMATOSUS
    ATTIAS, MR
    SYLVESTE.RA
    TALAL, N
    [J]. ARTHRITIS AND RHEUMATISM, 1973, 16 (06): : 719 - 725
  • [8] HYDRALAZINE DISEASE IN THE GUINEA-PIG AS AN EXPERIMENTAL MODEL FOR LUPUS ERYTHEMATOSUS
    BRAVERMAN, IM
    LERNER, AB
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1962, 39 (04) : 317 - 327
  • [9] BUDINSKY RA, 1987, DRUG METAB DISPOS, V15, P37
  • [10] AUTOANTIBODIES TO TYPE-II COLLAGEN - OCCURRENCE IN RHEUMATOID-ARTHRITIS, OTHER ARTHRITIDES, AUTOIMMUNE CONNECTIVE-TISSUE DISEASES, AND CHRONIC INFLAMMATORY SYNDROMES
    CHOI, EKK
    GATENBY, PA
    MCGILL, NW
    BATEMAN, JF
    COLE, WG
    YORK, JR
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 1988, 47 (04) : 313 - 322