Download PDF
Thromb Haemost 1997; 77(01): 011-013
DOI: 10.1055/s-0038-1655728
Rapid Communication
Schattauer GmbH Stuttgart

Autoantibodies Against the Protease Inhibitor Calpastatin: A New Risk Factor for Venous Thrombosis?

Udo Schlosser
The Institut für Klinische Chemie und Laboratoriumsmedizin, Universität Regensburg, Germany
,
Karl J Lackner
The Institut für Klinische Chemie und Laboratoriumsmedizin, Universität Regensburg, Germany
,
Christine Scheckenhofer
The Institut für Klinische Chemie und Laboratoriumsmedizin, Universität Regensburg, Germany
,
Michael Spannagl
1   The Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität Munchen, Germany
,
Florentin A Spengel
1   The Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität Munchen, Germany
,
Gabriele Hahn
2   The Department of Microbiology and Immunology, Stanford University, Stanford, CA
,
Bernhard Lang
3   The Klinik und Poliklinik fur Innere Medizin I, Universität Regensburg, Germany
,
Gerd Schmitz
The Institut für Klinische Chemie und Laboratoriumsmedizin, Universität Regensburg, Germany
› Author Affiliations
Further Information

Publication History

Received 18 April 1996

Accepted after resubmission 16 September 1996

Publication Date:
11 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Autoantibodies reactive against human calpastatin were detected by screening a cDNA expression library with the serum of a 53 year old white female patient with a history of venous thrombosis and suspected antiphospholipid syndrome. When further sera were analyzed it could be shown that >90% of calpastatin autoantibodies, detected by Western blotting against the partial calpastatin clone, react with the C-terminal amino acids of the protein. Therefore, an ELISA based on a synthetic peptide containing the C-terminal 27 amino acids of calpastatin was developed and 205 healthy blood donors and 138 random sera from hospital patients were analyzed. A total of 11 sera (3.2%) were positive with no significant difference between the two groups (7/205 and 4/138). In 80 consecutive patients with a history of venous thrombosis 9 positive sera (11.3%; p < 0.01 vs. blood donors, p<0.02 vs. hospital patients) were detected. Our results indicate that autoantibodies against calpastatin may constitute a so far unknown risk factor for venous thrombosis.

 

  • References

  • 1 Dahlbäck B. Molecular genetics of venous thromboembolism. Ann Med 1995; 27: 187-192
    CrossrefPubMedGoogle Scholar
  • 2 Nachman RL, Silverstein R. Hypercoagulable states. Ann Intern Med 1993; 119: 819-827
    CrossrefPubMedGoogle Scholar
  • 3 Hughes GRV. The antiphospholipid syndrome: ten years on. Lancet 1993; 342: 341-344
    CrossrefPubMedGoogle Scholar
  • 4 Cabiedes J, Cabral AR, Alarcón-Segovia D. Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-β2-glycoprotein-I than with antiphospholipid antibodies. J Rheumatol 1995; 22: 1899-1906
    PubMedGoogle Scholar
  • 5 Balestrieri G, Tincani A, Spatola L, Allegri F, Prati E, Cattaneo R, Valesini G, Del Papa N, Meroni P. Anti-beta2-glycoprotein I antibodies: a marker of antiphospholipid syndrome?. Lupus 1995; 04: 122-130
    CrossrefPubMedGoogle Scholar
  • 6 Vaarala o, Alfthan G, Jauhiainen M, Leirisalo-Repo M, Aho K, Palosuo T. Crossreaction between antibodies to oxidised low-density lipoprotein and to cardiolipin in systemic lupus erythematosus. Lancet 1993; 341: 923-925
    CrossrefPubMedGoogle Scholar
  • 7 Yamazaki M, Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Morishita E, Aoshima K, Ikeda T, Matsuda T. Plasma levels of lipoprotein(a) are elevated in patients with the antiphospholipid antibody syndrome. Thromb Haemost 1994; 71: 424-427
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Key NS. Toward an understanding of the pathophysiologic mechanism of thrombosis in the antiphospholipid antibody syndrome. J Lab Clin Med 1995; 125: 16-17
    PubMedGoogle Scholar
  • 9 Pötsch B, Kawamura H, Preissner KT, Schmidt M, Seelig C, Miiller-Berghaus G. Acquired protein C dysfunction but not decreased activity of thrombomodulin is a possible marker of thrombophilia in patients with lupus anticoagulant. J Lab Clin Med 1995; 125: 56-65
    PubMedGoogle Scholar
  • 10 Komberg A, Blank M, Kaufman S, Shoenfeld Y. Induction of tissue factorlike activity in monocytes by anti-cardiolipin antibodies. J Immunol 1994; 153: 1328-1332
    PubMedGoogle Scholar
  • 11 Croall DE, DeMartino GN. Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol Rev 1991; 71: 813-847
    CrossrefPubMedGoogle Scholar
  • 12 Despres N, Talbot G, Plouffe B, Boire G, Menard HA. Detection and expression of a cDNA clone that encodes a polypeptide containing two inhibitory domains of human calpastatin and its recognition by rheumatoid arthritis sera. J Clin Invest 1995; 95: 1891-1896
    CrossrefPubMedGoogle Scholar
  • 13 Mimori T, Suganuma K, Tanami Y, Nojima T, Matsumara M, Fujii T, Yoshizawa T, Suzuki K, Akizuki M. Autoantibodies to calpastatin (an endogenous inhibitor for calcium-dependent neutral protease, calpain) in systemic rheumatic diseases. Proc Natl Acad Sci USA 1995; 92: 7267-7271
    CrossrefPubMedGoogle Scholar
  • 14 Schlosser U, Lackner KJ, Scheckenhofer C, Schmitz G. Detection of autoantibodies against calpastatin, epitope mapping, and development of a specific peptide-ELISA. Clin Chem 1996; 42: 1250-7256
    PubMedGoogle Scholar
  • 15 Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of SLE. Arthritis Rheum 1982; 25: 1271-1277
    CrossrefPubMedGoogle Scholar
  • 16 Moore JC, Murphy WG, Kelton JG. Calpain proteolysis of von Willebrand factor enhances its binding to platelet membrane glycoprotein Ilb/IIIa: an explanation for platelet aggregation in thrombotic thrombocytopenic purpura. Br J Haematol 1990; 74: 457-464
    CrossrefPubMedGoogle Scholar
  • 17 Fox JEB, Austin CD, Reynolds CC, Steffen PK. Evidence that agonist-induced activation of calpain causes the shedding of procoagulant-containing micro vesicles from the membrane of aggregating platelets. J Biol Chem 1991; 266: 13289-13295
    PubMedGoogle Scholar
  • 18 Wang KKW, Yuen P-W. Calpain inhibition: an overview of its therapeutic potential. Trends Pharmacol Sci 1994; 15: 412-419
    CrossrefPubMedGoogle Scholar