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Thromb Haemost 1985; 53(01): 080-085
DOI: 10.1055/s-0038-1661241
Original Article
Schattauer GmbH Stuttgart

Measurement of Autoantibodies Against Fibrinogen and Fibrin Degradation Products by Enzyme-Linked Immunoassay

A N Whitaker
The University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia
,
J R McFarlane
The University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia
,
E A Rowe
The University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia
,
K Lee
The University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia
,
P P Masci
The University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia
› Author Affiliations
Further Information

Publication History

Received 10 May 1984

Accepted 08 November 1984

Publication Date:
18 July 2018 (online)

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Summary

We have devised a simple enzyme immunoassay to detect and quantitate autoantibodies against derivatives of fibrinogen. This assay has been applied with a range of antigens including a fibrinogen lysate (containing X, Y, D and E), D dimer, D dimerE and a preparation of high molecular weight complexes derived from crosslinked fibrin. We have found that autoantibodies interacting with these antigens can be detected in varying concentrations in most sera from both normal subjects and patients with a variety of diseases and are evidently of mixed Ig class. These autoantibodies are directed against at least several cryptic antigens which appear during fibrinogen/fibrin degradation and some appear to be directed specifically against cross- linked fibrin derivatives. No clear disease correlates have yet emerged but a relationship between elevated levels and prior infective, thrombotic, inflammatory or traumatic disorders is likely. It is suggested that these autoantibodies may contribute to the catabolism of fibrinogen derivatives, provide a marker of thrombosis, and sometimes produce pathologic effects.

Key words

Fibrin(ogen) degradation products - Autoimmunity - Intravascular coagulation - Enzyme-linked immunoassay
 

  • References

  • 1 Contreras CE, Orozco A, Sanchez P, Ortega G, Bianco NE. Physiological aspects of circulating immune complexes in the normal population. Clin Exp Immunol 1982; 48: 693-699
    PubMedGoogle Scholar
  • 2 Plow EF, Edgington TS. Immune responses to the cleavage- associated neoantigens of fibrinogen in man. Identification and characterization of humoral antibodies specific for cleavage fragments J Clin Invest 1975; 56: 1509-1518
    CrossrefPubMedGoogle Scholar
  • 3 Mammen EF, Schmidt KP, Barnhart MI. Thrombophlebitis migrans associated with circulating antibodies against fibrinogen. Thrombos Diathes Haemorrh 1967; 18: 605-611
    PubMedGoogle Scholar
  • 4 Hoots WK, Carrell NA, Wagner RH, Cooper HA, McDonagh J. A naturally occurring antibody that inhibits fibrin polymerization. N Engl J Med 1981; 304: 857-861
    CrossrefPubMedGoogle Scholar
  • 5 Ghosh S, McEvoy P, McVerry BA. Idiopathic autoantibody that inhibits fibrin monomer polymerization. Br J Haematol 1983; 53: 65-72
    CrossrefPubMedGoogle Scholar
  • 6 Plow EF, Edgington TS. Surface markers of fibrinogen and its physiologic derivatives revealed by antibody probes. Semin Thromb Haemostas 1982; 8: 36-56
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Whitaker AN, Elms MJ, Masci PP, Bundesen PG, Rylatt DB, Webber AJ, Bunce IH. Measurement of crosslinked fibrin derivatives in plasma: An immunoassay using monoclonal antibodies. J Clin Pathol 1984; 37: 882-887
    CrossrefPubMedGoogle Scholar
  • 8 Elms MJ, Bunce IH, Bundesen PG, Rylatt DB, Webber AJ, Masci PP, Whitaker AN. Measurement of crosslinked fibrin degradation products - An immunoassay using monoclonal antibodies. Thromb Haemostas 1983; 50: 591-594
    PubMedGoogle Scholar
  • 9 Rylatt DB, Blake AS, Cottis LE, Massingham DA, Fletcher WA, Masci PP, Whitaker AN, Elms M, Bunce I, Webber AJ, Wyatt D, Bundesen PG. An immunoassay for human D dimer using monoclonal antibodies. Thromb Res 1983; 31: 767-778
    CrossrefPubMedGoogle Scholar
  • 10 Cierniewski CS, Janiak A, Nowak P, Augustyniak W. Reactivity of fibrinogen derivatives with antisera to human fibrin D dimer and its γ-γ chain remnant. Thromb Haemostas 1982; 48: 33-37
    PubMedGoogle Scholar
  • 11 Gaffney PJ. Molecular aspects of fibrinolysis. Ann NY Acad Sci 1981; 370: 551-567
    CrossrefPubMedGoogle Scholar
  • 12 Sobel JH, Koehn JA, Friedman R, Canfield RE. Alpha chain crosslinking of human fibrin: Purification and radioimmunoassay development for two Aα chain regions involved in crosslinking. Thromb Res 1982; 26: 411-424
    CrossrefPubMedGoogle Scholar
  • 13 Takagi K, Kawai T. Radioimmunoassay of an early plasmin degradation product of human fibrinogen, “fragment A”, and its clinical application. Thromb Haemostas 1978; 39: 1-11
    PubMedGoogle Scholar
  • 14 Pacella Jr BL, Hui KY, Haber E, Matsueda GR. Induction of fibrin-specific antibodies by immunization with synthetic peptides that correspond to amino termini of thrombin cleavage sites. Mol Immunol 1983; 20: 521-527
    CrossrefPubMedGoogle Scholar
  • 15 Soria J, Soria C, Boucheix C, Mirshahi M, Perrot JY, Bernadou A, Samama M. Immunochemical differentiation of fibrinogen fragment D or and crosslinked fibrin degradation products using monoclonal antibodies. In “Fibrinogen - StructuresFunctional AspectsMetabolism”. Haverkate F, Henschen A, Nieuwenhuizen W, Straub PW. (Eds) Walter de Gruyter & Co; Berlin, New York: 1983. 2 227-233
    Google Scholar
  • 16 Plow EF, Gramse M, Havemann K. Immunochemical discrimination of leukocyte elastase from plasmic degradation products of fibrinogen. J Lab Clin Med 1983; 102: 858-869
    PubMedGoogle Scholar
  • 17 Deutsch DG, Mertz ET. Plasminogen: Purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096
    CrossrefPubMedGoogle Scholar
  • 18 Robbins KC, Summaria L. Plasminogen and plasmin. Methods Enzymol 1976; 45 (Part B) 257-273
    PubMedGoogle Scholar
  • 19 Saunders GC. The art of solid-phase immunoassay including selected protocols. In “Immunoassays in the Clinical Laboratory”. Nakamura RM, Dito WR, Tucker III ES, (Eds) Alan R. Liss Inc; New York: 1979. pp 99-118
    Google Scholar
  • 20 Porstmann B, Porstmann T, Gaede D, Nugel E, Egger E. Temperature dependent rise in activity of horseradish peroxidase caused by non-ionic detergents and its use in enzyme-immunoassay. Clin Chim Acta 1981; 109: 175-181
    CrossrefPubMedGoogle Scholar
  • 21 Galanakis DK, Ginzler EM, Fikrig SM. Monoclonal IgG anticoagulants delaying fibrin aggregation in two patients with systemic lupus erythematosus. Blood 1978; 52: 1037-1046
    PubMedGoogle Scholar
  • 22 DeVries A, Rosenberg T, Kochwa S, Boss J. Precipitating antifibrinogen antibody appearing after fibrinogen infusions in a patient with congenital afibrinogenemia. Am J Med 1961; 30: 486-494
    CrossrefPubMedGoogle Scholar
  • 23 Cheung K, O’Kane D, Robinson MF. Measurement of circulating immune complexes in human sera by enzyme immunoassay. Aust J Exp Biol Med Sci 1982; 60: 593-605
    PubMedGoogle Scholar
  • 24 MacKenzie AR. Non-trypanosome specific components of the elevated IgM levels in rabbit trypanosomiasis. Trans R Soc Trop Med Hyg 1972; 66: 344-345
    PubMedGoogle Scholar
  • 25 Boreham PF L, Facer CA. Autoimmunity in trypanosome infections. II. Anti-fibrin/fibrinogen (anti-F) autoantibody in Trypanosoma (Trypanozoon) brucei infections of the rabbit. Int J Parasitol 1974; 4: 601-607
    CrossrefPubMedGoogle Scholar
  • 26 Rickman WJ, Cox HW. Immunologic reactions associated with anaemia, thrombocytopenia, and coagulopathy in experimental African trypanosomiasis. J Parasitol 1980; 66: 28-33
    CrossrefPubMedGoogle Scholar
  • 27 Mahoney DF, Goodger BV. Serum changes in infected calves. Exp Parasitol 1969; 24: 375-382
    CrossrefPubMedGoogle Scholar
  • 28 Thoongsuwam S, Cox HW, Rickman WJ. Antibody to fibrinogen/ fibrin products (anti-F) in malaria, babesiosis, and trypanosomiasis of rodents. J Parasitol 1979; 65: 426-429
    CrossrefPubMedGoogle Scholar
  • 29 Sherman LA, Fletcher AP, Sherry S. In vivo transformation between fibrinogens of varying ethanol solubilities: a pathway of fibrinogen catabolism. J Lab Clin Med 1969; 73: 574-583
    PubMedGoogle Scholar
  • 30 Galanakis DK, Mosesson MW. Human fibrinogen heterogeneities: determination of the major Act chain derivatives in blood. Thromb Res 1983; 31: 403-413
    CrossrefPubMedGoogle Scholar
  • 31 Kalowski S, Howes EL, Margaretten W, McKay DG. Effects of intravascular clotting on the activation of the complement system. Am J Pathol 1975; 78: 525-536
    PubMedGoogle Scholar
  • 32 Gonzalo A, Mampaso F, Gallego N, Bellas C, Segui J, Ortuno J. Hemolytic uremic syndrome with hypocomplementemia and deposits of IgM and C3 in the involved renal tissue. Clin Nephrol 1981; 16: 193-199
    PubMedGoogle Scholar
  • 33 Barre P, Kaplan BS, Chadarevian de J-P, Drummond KN. Hemolytic uremic syndrome with hypocomplementemia, serum C3NeF, and glomerular deposits of C3. Arch Pathol Lab Med 1977; 101: 357-361
    PubMedGoogle Scholar
  • 34 Segonds A, Louradour N, Sue JM, Orfila C. Postpartum hemolytic uremic syndrome: A study of three cases with a review of the literature. Clin Nephrol 1979; 12: 229-242
    PubMedGoogle Scholar
  • 35 Houwert-de Jong MH, te Velde ER, Nefkens MJ J, Schuurman HJ. Immune complexes in skin of patients with pre-eclamptic toxaemia. Lancet 1982; 2: 387
    PubMedGoogle Scholar
  • 36 Crain SM, Choudhury AM. Thrombotic thrombocytopenic purpura: A reappraisal. JAMA 1981; 147: 1243-1246
    PubMedGoogle Scholar
  • 37 Whitaker AN, Bunce IH, Sleigh B. Thrombosis, pulmonary embolism and coagulation inhibitors in systemic lupus erythematosus. IRCS Med Sci 1978; 6: 197
    PubMedGoogle Scholar
  • 38 Wilner GD, Hsieh K-H, Thomas DW. Immunology of fibrinogen: Comparisons of serologic and cellular immune responses to human fibrinopeptide B (hFPB). Ann NY Acad Sci 1981; 370: 528-535
    CrossrefPubMedGoogle Scholar