DIFFERENCES BETWEEN HUMAN HYBRIDOMA PLATELET-BINDING ANTIBODIES DERIVED FROM SYSTEMIC LUPUS-ERYTHEMATOSUS PATIENTS AND NORMAL INDIVIDUALS

被引:11
作者
MENG, QH [1 ]
RAUCH, J [1 ]
机构
[1] MCGILL UNIV,MONTREAL GEN HOSP,RES INST,RHEUMAT DIS UNIT,1650 CEDAR AVE,MONTREAL H3G 1A4,QUEBEC,CANADA
基金
英国医学研究理事会;
关键词
Anti-phospholipid; Hybridoma autoantibodies; Normal; Platelet-binding; Polyspecificity; SLE;
D O I
10.3109/08916939009002974
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The binding and functional activities of platelet-binding hybridoma autoantibodies from SLE patients were compared with those derived from normal individuals. Twenty-nine SLE-derived hybridoma antibodies and 20 normal-derived hybridoma antibodies were analyzed for binding to glutaraldehyde fixed platelets, dDNA and phospholipids, and for lupus anticoagulant activity. Twenty-four of the 29 SLE-derived antibodies and 9 of the 20 normal-derived antibodies showed one or more activities in these assays. Of the 24 SLE-derived antibodies, 8 (33.3% were reactive in only one assay (monospecific), while the other 16 (66.7% had more than one of these activities (polyspecific). In contrast, none (0% of the 9 normal-derived antibodies with known activities were monospecific, while all 9 (100% showed polyspecificity. Statistical analyses demonstrated that there was no correlation of anti-DNA activity with anti-platelet and most anti-phospholipid activities for the SLE-derived antibodies, and strong positive correlations between these reactivities for the normal-derived antibodies. Similarly, differences were observed in Western blotting analyses; SLE-derived antibodies bound more specifically to individual platelet proteins than normal-derived antibodies. Moreover, in chromium-51 release assays, all of the SLE-derived platelet-binding antibodies were cytotoxic to platelets, while none of the normal-derived platelet-binding antibodies showed significant cytotoxicity. Our results suggest that hybridoma platelet-binding autoantibodies derived from SLE patients exhibit greater antigen specificity and functional activity than similar antibodies derived from normal individuals. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
引用
收藏
页码:151 / 167
页数:17
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共 33 条
  • [1] Avrameas S., Guilbert B., Dighiero G., Natural antibodies against tubulin, actin, myoglobulin, thyro-globulin, fetuin, albumin, and transferrin are present in normal human sera, and monoclonal immunoglobulins from multiple myeloma and Waldenstrom's macroglobulinemia may express similar antibody specificities, Ann Immunol (Inst Pusteur), 132C, pp. 231-236, (1981)
  • [2] Guilbert B., Dighiero G., Avrameas S., Naturally occurring antibodies against nine common antigens in human sera. I. Detection, isolation and characterization, J Immunol, 128, pp. 2779-2787, (1982)
  • [3] Dighiero G., Guilbert B., Avrameas S., Naturally occurring antibodies against nine common antigens in humans. II. High incidence of monoclonal Ig exhibiting antibody activity against actin and tubulin and sharing antibody specifications with natural antibodies, J Immunol, 128, pp. 2788-2792, (1982)
  • [4] Madaio M.D., Schattner A., Schattner M., Schwartz R.S., Lupus serum and normal human serum containing anti-DNA antibodies with the same idiotype marker, J Immunol, 137, pp. 2535-2540, (1986)
  • [5] Dighiero G., Lymberi P., Holmberg D., Lundquist I., Coutinho A., Avrameas S., High frequency of natural autoantibodies in normal newborn mice, J Immunol, 134, pp. 765-771, (1985)
  • [6] Holmberg D., Freitas A.A., Portnoi D., Jacquemart F., Avrameas S., Coutinho A., Antibody repertoires of normal BALB/c mice: B lymphocyte populations defined by state of activation, Immunol Rev, 93, pp. 147-169, (1986)
  • [7] Holmberg D., Forsgren S., Ivars F., Coutinho A., Reactions among IgM antibodies derived from normal, neonatal mice, Eur J Immunol, 14, pp. 435-441, (1984)
  • [8] Vakil M., Dearney J.F., Functional characterization of monoclonal auto-anti-diotype antibodies isolated from the early B cell repertoire of BALB/c mice, Eur J Immunol, 16, pp. 1151-1158, (1986)
  • [9] Cairns E., Block J., Bell D.A., Anti-DNA autoantibody-producing hybridomas of normal human lymphoid cell origin, J Clin Invest, 74, pp. 880-887, (1984)
  • [10] Cairns E., Komar R., Bell D.A., Cytoskeletal binding of monoclonal anti-DNA antibodies derived from tonsillar lymphoid cells of a normal subject, Arthritis Rheum, 29, pp. 1351-1358, (1986)