Thromb Haemost 1990; 64(01): 021-025
DOI: 10.1055/s-0038-1647147
Original Article
Schattauer GmbH Stuttgart

Clinical Significance of Various ELISA Assays for Detecting Antiphospholipid Antibodies[*]

C R Falcón
The Haemostasis and Thrombosis Section, Division of Haematology, Hospital de Clinicas, University of Buenos Aires, Argentina
,
A M Hoffer
The Haemostasis and Thrombosis Section, Division of Haematology, Hospital de Clinicas, University of Buenos Aires, Argentina
,
R R Forastiera
The Haemostasis and Thrombosis Section, Division of Haematology, Hospital de Clinicas, University of Buenos Aires, Argentina
,
L O Carreras
The Haemostasis and Thrombosis Section, Division of Haematology, Hospital de Clinicas, University of Buenos Aires, Argentina
› Author Affiliations
Further Information

Publication History

Received 08 September 1989

Accepted after revision 12 March 1990

Publication Date:
25 July 2018 (online)

Summary

We have compared the prevalence of antiphospholipid antibodies (APA) measured by enzyme-linked immunosorbent assay (ELISA), in 119 selected patients using five different antigens: bovine cardiolipin, phosphatidylserine, phosphatidylinositol, bovine partial thromboplastin and human brain partial thromboplastin. All the plasmas have been evaluated for the presence of lupus anticoagulant (LA) activity by clotting techniques. We found a significant association between the incidence of LA and APA (p <0.001), only moderate agreement between the prolongation of the activated partial thromboplastin time (APTT) and ELISAs (r around 0.50) and a good agreement between the ELISAs (r around 0.80). The combination of antibodies against cardiolipin (ACA) and human brain partial thromboplastin (AHPTA) allowed the detection of antibodies in most of the LA positive cases. ACA, AHPTA and antiphosphatidylinositol antibodies detected all the positive samples. Six patients (5%) had a single APA detected. The clinical associations of APA according to phospholipid specificity, immunoglobulin isotype and titer are shown.

Dedicated to Professor Marc Verstraete on the occasion of his 65th birthday.


 
  • References

  • 1 Lechner K. Acquired inhibitors in nonhemophilic patients. Haemostasis 1974; 3: 65-93
  • 2 Mueh JR, Herbst KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980; 92: 156-159
  • 3 Lechner K, Pabinger-Fasching I. Lupus anticoagulants and thrombosis: A study of 25 cases and review of the literature. Haemostasis 1985; 15: 254-262
  • 4 Elias M, Eldor A. Thromboembolism in patients with the “lupus”-like circulating anticoagulant. Arch Int Med 1984; 144: 510-515
  • 5 Firkin BG, Howard MA, Radford N. Possible relationship between lupus inhibitor and recurrent abortion in young women. Lancet 1980; 2: 366
  • 6 Branch WD, Scott JR, Kochenour NK, Hershgold E. Obstetric complications associated with lupus anticoagulant. N Engl J Med 1985; 313: 1322-1326
  • 7 Carreras LO, Defreyn G, Machin SJ, Vermylen J, Deman R, Spitz B, Van Assche A. Recurrent arterial thrombosis, intrauterine death and “lupus” anticoagulant: Detection of immunoglobulin interfering with prostacyclin production. Lancet 1981; 1: 244-246
  • 8 Carreras LO, Vermylen J, Spitz B, Van Assche A. “Lupus” anticoagulant and inhibition of prostacyclin formation in patients with repeated abortion, intrauterine growth retardation and intrauterine death. Br J Obstet Gynaecol 1981; 88: 890-894
  • 9 De Wolf F, Carreras LO, Moerman P, Vermylen J, Van Assche A, Renaer M. Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant. Am J Obstet Gynecol 1982; 142: 829-834
  • 10 Harris EN, Asherson RA, Gharavi AE, Morgan SM, Derue G, Hughes GR V. Thrombocytopenia in SLE and related autoimmune disorders. Association with anti-cardiolipin antibody. Br J Haematol 1985; 59: 227-230
  • 11 Lechner K. Lupus anticoagulants and thrombosis. In: Thrombosis and Haemostasis Verstraete M, Vermylen J, Lijnen HR, Arnout J. (eds). International Society on Thrombosis and Haemostasis and Leuven University Press; Leuven: 1987: 525-547
  • 12 Hughes GR V, Harris EN, Gharavi AE. The anticardiolipin syndrome. J Rheumatol 1986; 13: 486-489
  • 13 Harris EN, Baguley E, Asherson RA, Gharavi AE, Hughes GR V. The antiphospholipid syndrome: definition and clinical features (abstract). Proc III Int Symp Antiphospholipid Antibodies and Thrombosis Kingston, Jamaica: 1988
  • 14 Harris EN, Gharavi AE, Tincani A, Chan JK K, Englert H, Mantelli P, Allegro F, Ballestrieri G, Hughes GR V. Affinity purified anti-cardiolipin and anti-DNA antibodies. J Clin Lab Immunol 1985; 17: 155-162
  • 15 Violi F, Valesini G, Ferro D, Tincani A, Ballestrieri G, Balsano F. Anticoagulant activity of anticardiolipin antibodies. Thromb Res 1986; 44: 543-547
  • 16 Loizou S, McCrea JD, Rudge AC, Reynolds R, Boyle CC, Harris EN. Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. Clin Exp Immunol 1985; 62: 738-745
  • 17 Branch DW, Rote NS, Scott JR. The demonstration of lupus anticoagulant by an enzyme-linked immunosorbent assay. Clin Immunol Immunopathol 1986; 39: 298-307
  • 18 Branch DW, Rote NS, Dostal DA, Scott JR. Association of lupus anticoagulant with antibody against phosphatidylserine. Clin Immunol Immunopathol 1987; 42: 63-75
  • 19 Harris EN, Gharavi AE, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GR V. Anticardiolipin antibodies: Detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2: 1211-1214
  • 20 Derksen RH W M, Hasselaar P, Blokzijl L, Gmelig Meyling JH J, De Groot PG. Coagulation screen is more specific than the anticardioli-pin antibody ELISA in defining a thrombotic subset of lupus patients. Ann Rheum Dis 1988; 47: 364-371
  • 21 Tan EM, Cohen AS, Fries JF, Masi AT, Me Shane DJ, Ruthfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-1277
  • 22 Exner T, Rickard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1977; 40: 143-151
  • 23 Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood 1986; 68: 869-874
  • 24 Triplett DA, Brandt JT, Kaczor D, Schaefer J. Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure. Am J Clin Pathol 1983; 79: 678-682
  • 25 Rosove MH, Ismail M, Koriol BJ, Runge A, Kasper CK. Lupus anticoagulants: improved diagnosis with a kaolin clotting time using rabbit brain phospholipid in standard and high concentrations. Blood 1986; 68: 472-478
  • 26 Rosner E, Pauzner R, Lusky A, Modan M, Many A. Detection and quantitative evaluation of lupus circulating anticoagulant activity. Thromb Haemostas 1987; 57: 144-147
  • 27 Green D, Hougie C, Kazmier FJ, Lechner K, Mannucci PM, Rizza CR, Sultan Y. Report of the Working Party on Acquired Inhibitors of Coagulation: Studies of “lupus” anticoagulant. Thromb Haemostas 1983; 49: 144-146
  • 28 Larrieu MJ, Willard C. Utilization de la cephaline dans les tests de coagulation. Rev Hematol 1957; 12: 199
  • 29 Harris EN, Hughes GR V. Standardizing the anti-cardiolipin antibody test. Lancet 1987; 1: 277
  • 30 Mann KG, Tracy PB, Nesheim ME. Assembly and function of prothrombinase complex on synthetic and natural membranes. In: Interaction of Platelets with the Vessel Wall Oates JA, Hawiger J, Ross R. (eds). Waverly Press; Baltimore, MD: 1985: 48
  • 31 Rittenhouse-Simmons S. Production of diglyceride from phosphatidyl-inositol in activated human platelets. J Clin Invest 1979; 63: 580-587
  • 32 Schorer AE, Wickham NW R, Watson KV. Lupus anticoagulant induces a selective defect in thrombin-mediated endothelial prostacyclin release and platelet aggregation. Br J Haematol 1989; 71: 399-407
  • 33 Lopez-Soto A, Casals FJ, Font J, Cervera R, Ingelmo M. Detection of antiphospholipid antibodies by ELISA-method with bovine thromboplastin as antigen. Thromb Res 1989; 53: 623-628
  • 34 Harris EN, Loizou S, Engler H. Anticardiolipin antibodies and lupus anticoagulant. Lancet 1984; 2: 1099
  • 35 Triplett DA, Brandt JT, Musgrave KA, Orr CA. The relationship between lupus anticoagulants and antibodies to phospholipid. JAMA 1988; 259: 550-554
  • 36 Thiagarajan P, Shapiro SS, De Marco L. Monoclonal immunoglobulin MX coagulation inhibitor with phospholipid specificity: Mechanism of a lupus anticoagulant. J Clin Invest 1980; 66: 397-405
  • 37 Pengo V, Thiagarajan P, Shapiro S, Heine M. Immunological specificity and mechanism of action of IgG lupus anticoagulants. Blood 1987; 70: 69-76
  • 38 Gharavi AE, Harris EN, Asherson RA, Hughes GR V. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis 1987; 46: 1-6
  • 39 Weidman CE, Wallace DJ, Peter JB, Knight PJ, Bear MB, Klinenberg JR. Studies of IgG, IgM and IgA antiphospholipid antibody isotypes in systemic lupus erythematosus. J Rheumatol 1988; 15: 74-79
  • 40 Walker TS, Triplett DA, Javed N, Musgrave K. Evaluation of lupus anticoagulants: antiphospholipid antibodies, endothelium associated immunoglobulin, endothelial prostacyclin secretion, and antigenic protein S levels. Thromb Res 1988; 51: 267-281
  • 41 Harris EN, Gharavi AE, Hughes GR V. Antiphospholipid antibodies. Clin Rheum Dis 1985; 11: 591-609
  • 42 Harris EN, Chan JK, Asherson RA, Aber VR, Gharavi AE, Hughes GR V. Thrombosis, recurrent fetal loss and thrombocytopenia. Predictive value of the anticardiolipin antibody test. Arch Intern Med 1986; 146: 2153-2156
  • 43 Norberg R, Nived O, Sturfelt G, Unander M, Arfors L. Anticardiolipin and complement activation: relation to clinical symptoms. J Rheumatol 1987; 14: 149-153
  • 44 Lockshin MD, Druzin ML, Goei S. Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus. N Engl J Med 1985; 313: 152-156
  • 45 Fort JG, Cowchock FS, Abruzzo JL, Smith B. Anticardiolipin antibodies in patients with rheumatic diseases. Arthritis Rheum 1987; 30: 752-760
  • 46 Kalunian KC, Peter JB, Middlekauff HR, Sayre J, Ando DG, Mongotich M, Hahn BH. Clinical significance of a single test for anticardiolipin antibodies in patients with systemic lupus erythematosus. Am J Med 1988; 85: 602-608
  • 47 Cronin ME, Biswas RM, Van der Straeton C, Fleisher TA, Klippel JH. IgG and IgM anticardiolipin antibodies in patients with lupus with anticardiolipin antibody associated clinical syndromes. J Rheumatol 1988; 15: 795-798
  • 48 Colaco CB, Male DK. Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: distinct profiles of epitope specificity. Clin Exp Immunol 1985; 59: 449-456
  • 49 Manoussakis MN, Gharavi AE, Drosos AA, Kitridou RC, Moutsopoulos HM. Anticardiolipin antibodies in unselected autoimmune rheumatic disease patients. Clin Immunol Immunopathol 1987; 44: 297-307
  • 50 Sturfelt G, Nived O, Norberg R, Thorstensson R, Krook K. Anticardiolipin antibodies in patients with systemic lupus erythematosus. Arthritis Rheum 1987; 30: 382-388
  • 51 Hazeltine M, Rauch J, Danoff D, Esdaile JM, Tannenbaum H. Antiphospholipid antibodies in systemic lupus erythematosus: evidence of an association with positive Coombs’ and hypocomplement-emia. J Rheumatol 1988; 15: 80-86
  • 52 Petri M, Rheinschmidt M, Whiting-O’Keefe Q, Hellmann D, Corash L. The frequency of lupus anticoagulant in systemic lupus erythematosus. Ann Intern Med 1987; 106: 524-531