Download PDF
Thromb Haemost 2001; 85(05): 800-805
DOI: 10.1055/s-0037-1615751
Review Article
Schattauer GmbH

Antibodies to Phosphatidylethanolamine as the only Antiphospholipid Antibodies Found in Patients with Unexplained Thromboses

Marielle Sanmarco
1   Fédération Autoimmunité-Thrombose, Laboratoire d’Immunologie, Hôpital de La Conception, CHU
,
Marie-Christine Alessi
2   Laboratoire d’Hématologie, Hôpital de La Timone, CHU
,
Jean Robert Harle
3   Service de Médecine Interne, Hôpital de La Conception, CHU
,
Christophe Sapin
4   Laboratoire de Santé Publique, Faculté de Médecine, CHU
,
Marie-Françoise Aillaud
2   Laboratoire d’Hématologie, Hôpital de La Timone, CHU
,
Stéphanie Gentile
4   Laboratoire de Santé Publique, Faculté de Médecine, CHU
,
Irène Juhan-Vague
2   Laboratoire d’Hématologie, Hôpital de La Timone, CHU
,
Pierre-Jean Weiller
5   Service de Médecine Interne, Hôpital de La Timone, CHU, Marseille, France
› Author Affiliations
Further Information

Publication History

Received 24 July 2000

Accepted after resubmission 28 December 2000

Publication Date:
11 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

The objective of this study was to assess the interest of antiphosphatidylethanolamine antibodies (aPE) in unexplained thrombosis (UT) defined as thrombotic episode without any of the main autoimmune and hereditary thrombophilic defects. Results from 98 UT were compared to those of (I) 142 patients with thrombophilia: 67 antiphospholipid syndrome (APS) and 75 hereditary hemostatic defects (HHD); (II) 110 patients without thrombosis: 60 with systemic lupus erythematosus (SLE) and 50 with infectious diseases (ID). As compared to controls (100 blood donors), aPE prevalence was significantly higher in both autoimmune contexts (APS: 43%; SLE: 40%, p <0.0001) and among non-autoimmune pathologies, only in UT (18%, p = 0.001) conversely to HHD (8%) or ID (10%). aPE prevalence in UT was not statistically different from that found in Primary APS (32%, p = 0.076) but lower than in Secondary APS (65%, p <0.005). In UT, aPE were mainly of IgM isotype like in Primary APS and they were found alone whereas in SLE they were always associated with classical anti-phospholipid antibodies. No significant association was found between any isotype of aPE and a site of thrombosis in UT as well as in APS. In conclusion, this study demonstrates an increase of the prevalence of aPE in patients with unexplained thrombosis. Thus, aPE investigation appears to be of interest in UT and their persistent presence could define a biological variant of APS.

Keywords

Thrombosis - antiphospholipid syndrome - antiphospholipid antibodies - antiphosphatidylethanolamine antibodies
 

  • References

  • 1 Harris EN, Baguley E, Asherson RA, Hughes GRV. Clinical and serological features of the “antiphospholipid syndrome”. Br J Rheumatol 1987; 26 (Suppl. 02) 19.
    PubMedGoogle Scholar
  • 2 Roubey RAS. Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulant and other “antiphospholipid” autoanti-bodies. Blood 1994; 84: 2854-67.
    PubMedGoogle Scholar
  • 3 McIntyre JA, Wagenknecht DR, Sugi T. Phospholipid binding plasma proteins required for antiphospholipid antibody detection-An overview. Am J Reprod Immunol 1997; 37: 101-10.
    CrossrefPubMedGoogle Scholar
  • 4 Cabral AR, Amigo MA, Cabiedes J, Alarcon-Segovia D. The antiphospholipid/cofactor syndromes: a primary variant with anti-β2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays. Am J Med 1996; 101: 472-81.
    CrossrefPubMedGoogle Scholar
  • 5 Tsutsumi A, Ichikawa K, Matsuura E, Koike T. Use of various methods for anticardiolipin detection in the updated American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum [letter] 1998; 41: 1326-7.
    CrossrefPubMedGoogle Scholar
  • 6 Staub HL, Harris EN, Khamashta MH, Savidge G, Chahade WH, Hughes GRV. Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis. Ann Rheumatol Dis 1989; 48: 166-9.
    CrossrefPubMedGoogle Scholar
  • 7 Falcon CR, Hoffer AM, Carreras LO. Evaluation of the clinical and laboratory associations of antiphosphatidylethanolamine antibodies. Thromb Res 1990; 59: 383-8.
    CrossrefPubMedGoogle Scholar
  • 8 Vlachoyiannopoulos PG, Beigbeder G, Dueymes M, Youinou P, Hunt JE, Krilis SA, Moutsopoulos HM. Antibodies to phosphatidylethanolamine in antiphospholipid syndrome and systemic lupus erythematosus: their correlation with anticardiolipin antibodies and 2-glycoprotein plasma levels. Autoimmunity 1993; 16: 245-9.
    CrossrefPubMedGoogle Scholar
  • 9 Karmochkine M, Berard M, Piette JC, Cacoub P, Aillaud MF, Harlet JR, Godeau P, Boffa MC. Antiphosphatidylethanolamine antibodies in systemic lupus erythematosus. Lupus 1993; 2: 157-60.
    CrossrefPubMedGoogle Scholar
  • 10 Berard M, Chantome R, Marcelli A, and Boffa MC. Antiphosphatidylethanolamine antibodies as the only antiphospholipid antibodies. I. Association with thrombosis and vascular cutaneous diseases. J Rheumatol 1996; 23: 1369-74.
    PubMedGoogle Scholar
  • 11 Gris JC, Quere I, Sanmarco M, Boutiere B, Mercier E, Amiral A, Hubert AM, Ripart-Neveu S, Hoffet M, Tailland ML, Rousseau O, Monpeyroux F, Dauzat M, Sampol J, Daures JP, Berland J, Mares P. Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early fœtal loss. Thromb Haemost 2000; 84: 228-36.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Sugi T, Katsunuma J, Izumi SI, McIntyre JA, Makino T. Prevalence and heterogeneity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses. Fertil Steril 1999; 71: 1060-5.
    CrossrefPubMedGoogle Scholar
  • 13 Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.
    PubMedGoogle Scholar
  • 14 Sanmarco M, Soler C, Christides C, Raoult D, Weiller PJ, Gerolami V, and Bernard D. Prevalence and clinical significance of IgG-isotype anti-β2-glycoprotein I antibodies in antiphospholipid syndrome: a comparative study with anticardiolipin antibodies. J lab Clin Med 1997; 129: 499-506.
    CrossrefPubMedGoogle Scholar
  • 15 Verrot D, Sanmarco M, Dravet C, Genton P, Disdier P, Bolla G, Harle JR, Reynaud L, Weiller PJ. Prevalence and Signification of Antinuclear and Anticardiolipin Antibodies in Patients with Epilepsy. Am J Med 1997; 103: 33-7.
    CrossrefPubMedGoogle Scholar
  • 16 Working Group on Hemostasis of the Société Française de Biologie Clinique.. Comparison of the standardized procedure with current laboratory practices for the detection of lupus anticoagulant in France. Thromb Haemost 1993; 70: 781-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Ordi-Ros J, Balada E, Martinez N, Paredes J, Villarreal J, Labrador M, Vilardell M. Antiphosphatidylethanolamine antibodies as a marker for the antiphospholipid syndrome [abstract]. Lupus 1998; 7 (Suppl. 02) B033.
    PubMedGoogle Scholar
  • 18 McMurray RW, Elbourne K. Hepatitis C virus infection and autoimmunity. Semin Arthritis Rheum 1997; 26: 689-701.
    CrossrefPubMedGoogle Scholar
  • 19 Coll Daroca J, Gutierrez-Cebollada J, Yazbeck H, Berges A, Rubies-Prat J. Anticardiolipin antibodies and acquired immunodeficiency syndrome: prognostic marker or association with HIV infection?. Infection 1992; 20: 140-2.
    CrossrefPubMedGoogle Scholar
  • 20 Berard M, Boffa MC. Influence of the phosphatidylethanolamine (PE) and bovine serum origins on anti-PE antibody detection by ELISA. Thromb Res 1997; 85: 439-42.
    CrossrefPubMedGoogle Scholar
  • 21 Sugi T, McIntyre JA. Autoantibodies to Phosphatidylethanolamine (PE) Recognize a Kininogen-PE Complex. Blood 1995; 86: 3083-9.
    PubMedGoogle Scholar
  • 22 Sugi T, McIntyre JA. Phosphatidylethanolamine induces specific conformational changes in the Kininogens recognizable by antiphosphatidylethanolamine antibodies. Thromb Haemost 1996; 76: 354-60.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Bounameaux H, Reber-Wasem MA. Superficial thrombophlebitis and deep vein thrombosis. A controversial association. Arch Intern Med 1997; 157: 1822-4.
    CrossrefPubMedGoogle Scholar
  • 24 Samlaska CP, James WD. Superficial thrombophlebitis. II. Secondary hypercoagulable states. J Am Acad Dermatol 1990; 23: 1-18.
    CrossrefPubMedGoogle Scholar
  • 25 Piette JC. Towards improved criteria for the antiphospholipid syndrome. Lupus 1998; 7 (Suppl. 02) 149-57.
    CrossrefPubMedGoogle Scholar
  • 26 Brey RL, Escalante A. Neurological manifestations of antiphospholipid antibody syndrome. Lupus 1998; 7 (Suppl. 02) 67-74.
    CrossrefPubMedGoogle Scholar
  • 27 Smirnov MD, Triplett DT. On the role of phosphatidylethanolamine in the inhibition of activated protein C activity by antiphospholipid antibodies. J Clin Invest 1995; 95: 309-16.
    CrossrefPubMedGoogle Scholar
  • 28 Borrell M, Sala N, de Castellarnau C, Lopez S, Gari M, Fontcuberta J. Immunoglobulin fractions isolated from patients with antiphospholipid antibodies prevent the inactivation of factor Va by activated protein C on human endothelial cells. Thromb Haemost 1992; 68: 268-72.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Smirnov MD, Ford DA, Esmon CT, Esmon NL. The effect on membrane composition on the hemostatic balance. Biochemistry 1999; 38: 3591-8.
    CrossrefPubMedGoogle Scholar