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Thromb Haemost 2002; 87(04): 599-605
DOI: 10.1055/s-0037-1613055
Review Article
Schattauer GmbH

Distinguishing Features of Anti-β2 Glycoprotein I Antibodies between Patients with Leprosy and the Antiphospholipid Syndrome

J. Arvieux
1   Laboratoire d’Immunologie, Institut de Synergie des Sciences et de la Santé, CHU Brest, France
,
Y. Renaudineau
1   Laboratoire d’Immunologie, Institut de Synergie des Sciences et de la Santé, CHU Brest, France
,
I. Mane
2   Institut de Léprologie Appliquée, Dakar, Sénégal
,
R. Perraut
3   Institut Pasteur, Dakar, Sénégal, New South Wales, Australia
,
S. A. Krilis
4   Department of Immunology, Allergy and Infectious Diseases, St George Hospital, Kogarah, New South Wales, Australia
,
P. Youinou
1   Laboratoire d’Immunologie, Institut de Synergie des Sciences et de la Santé, CHU Brest, France
› Author Affiliations
Further Information

Publication History

Received 14 November 2001

Accepted 28 December 2001

Publication Date:
08 December 2017 (online)

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Summary

Anticardiolipin (ACA), anti-β2 glycoprotein I (β2GPI), and antiprothrombin antibodies of IgG and IgM classes were quantitated by enzyme-linked immunosorbent assays in 176 untreated leprosy patients across the histopathological spectrum. Positivity rates ranged from 21% (IgG ACA) to 30% (IgM anti-prothrombin) versus 4% in healthy controls (p <10-2 to 10-3). Levels of IgM anti-β2GPI and IgG ACA were significantly higher in lepromatous leprosy and multibacillary patient subgroups. IgG3 was the most common subclass reactive to both β2GPI and prothrombin in selected high-titer leprosy sera, unlike antibodies from patients with the antiphospholipid syndrome (APS) largely restricted to IgG2. In leprosy patients, but not in the APS control group, there was no statistical correlation between ACA and anti-β2GPI antibody levels. Likewise, a large fraction of anti-β2GPI positive sera (36/45 and 28/44 for IgG and IgM, respectively) were unreactive in the standard ACA assay. Most assayed anti-β2GPI antibodies from leprosy patients showed (i) ability to recognize both human and bovine β2GPI immobilized on non-irradiated polystyrene plates, (ii) concentrationdependent inhibition of binding by cardiolipin, and (iii) relatively high avidity binding to fluid-phase β2GPI, thereby differing from those found in APS. Finally, the location of the major epitopic region on the β2GPI molecule targeted by autoantibodies was different in leprosy and APS, as assessed by direct binding to domain Iand V-deleted mutants and competition with the mouse monoclonal antibody 8C3, directed at domain I. Thus, leprosy-related antiphospholipid antibodies comprise persistent IgG and IgM anti-β2GPI that differ from APS-related ones with respect to IgG subclass, avidity and epitope specificity, possibly reflecting distinct pathophysiological significance.

Keywords

Antiphospholipid syndrome - leprosy - β2 glycoprotein I - prothrombin
 

  • References

  • 1 Britton WJ. The immunology of leprosy. Trans R Soc Trop Med Hyg 1993; 46: 508-14.
    PubMedGoogle Scholar
  • 2 Guedes LSBarbosa, Gilbrut B, Shoenfeld Y, Scheinberg MA. Autoantibodies in leprosy sera. Clin Rheumatol 1996; 15: 26-8.
    CrossrefPubMedGoogle Scholar
  • 3 Ridley D, Jopling M. Classification of leprosy according to immunity A five-group system. Int J Lepr Other Mycobact Dis 1966; 34: 255-73.
    PubMedGoogle Scholar
  • 4 Kandiah DA, Sali A, Sheng Y, Victoria EJ, Marquis DM, Coutts SM, Krilis SA. Current insights into the “antiphospholipid” syndrome: clinical, immunological, and molecular aspects. Adv Immunol 1998; 70: 507-63.
    PubMedGoogle Scholar
  • 5 McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49: 193-280.
    PubMedGoogle Scholar
  • 6 Galli M, Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome. Blood 1999; 93: 2149-57.
    PubMedGoogle Scholar
  • 7 Roubey RAS. Immunology of the antiphospholipid syndrome: antibodies, antigens, and autoimmune response. Thromb Haemost 1999; 82: 656-61.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Arvieux J, Pouzol P, Roussel B, Jacob MC, Colomb MG. Lupus-like anticoagulant properties of murine monoclonal antibodies to β2-glycoprotein I. Br J Haematol 1992; 81: 568-73.
    CrossrefPubMedGoogle Scholar
  • 9 Arvieux J, Darnige L, Caron C, Reber G, Bensa JC, Colomb MG. Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants. Thromb Haemost 1995; 74: 1120-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Loizou S, Cazabon JK, Walport MJ, Tait D, So AK. Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus. Arthritis Rheum 1997; 40: 103-8.
    CrossrefPubMedGoogle Scholar
  • 11 Hunt JE, McNeil P, Morgan GJ, Crameri RM, Krilis SA. A phospholipid-β2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. Lupus 1992; 01: 75-81.
    CrossrefPubMedGoogle Scholar
  • 12 de Larranaga GF, Forastiero RR, Martinuzzo ME, Carreras LO, Tsariktsian G, Sturno MM, Alonso BS. High prevalence of antiphospholipid antibodies in leprosy: evaluation of antigen reactivity. Lupus 2000; 09: 594-600.
    CrossrefPubMedGoogle Scholar
  • 13 Elbeialy A, Strassburger-Lorna K, Atsumi T, Bertolaccini ML, Amengual O, Hanafi M, Khamashta MA, Hughes GRV. Antiphospholipid antibodies in leprotic patients: a correlation with disease manifestations. Clin Exp Rheumatol 2000; 18: 492-4.
    PubMedGoogle Scholar
  • 14 Fiallo P, Travaglino C, Nunzi E, Cardo PP. β2-glycoprotein I-dependence of anticardiolipin antibodies in multibacillary leprosy patients. Lepr Rev 1998; 69: 376-81.
    PubMedGoogle Scholar
  • 15 Hojnik M, Gilburd B, Ziporen L, Blank M, Tomer Y, Scheinberg MA, Tincani A, Rozman B, Shoenfeld Y. Anticardiolipin antibodies in infections are heterogenous in their dependency on β2-glycoprotein I: analysis of anticardiolipin antibodies in leprosy. Lupus 1994; 03: 515-21.
    CrossrefPubMedGoogle Scholar
  • 16 Mane I, Cartel JL, Grosset JH. Field trial on efficacy of supervised monthly dose of 600 mg rifampin, 400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first results. Int J Leprosy 1997; 65: 224-9.
    PubMedGoogle Scholar
  • 17 Wilson WA, Gharavi AE, Piette JC. International classification criteria for antiphospholipid syndrome: synopsis of a post-conference workshop held at the ninth international (Tours) aPL symposium. Lupus 2001; 10: 457-60.
    CrossrefPubMedGoogle Scholar
  • 18 Arvieux J, Regnault V, Hachulla E, Darnige L, Roussel B, Bensa JC. Heterogeneity and immunochemical properties of anti-β2-glycoprotein I autoantibodies. Thromb Haemost 1998; 80: 393-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Sheng Y, Kandiah DA, Krilis SA. Anti-β2-glycoprotein I autoantibodies from patients with the “antiphospholipid” syndrome bind to β2-glycoprotein I with low affinity: dimerization of β2-glycoprotein I induces a significant increase in anti-β2-glycoprotein I antibody affinity. J Immunol 1998; 161: 2038-43.
    PubMedGoogle Scholar
  • 20 Arvieux J, Roussel B, Ponard D, Colomb MG. IgG2 subclass restriction of anti-β2 glycoprotein I antibodies in autoimmune patients. Clin Exp Immunol 1994; 95: 310-5.
    PubMedGoogle Scholar
  • 21 Bouma B, de Groot PG, van den Elsen JMH, Ravelli RBG, Schouten A, Simmelink MJA, Derksen RHWM, Kroon J, Gros P. Adhesion mechanism of human β2-glycoprotein I to phospholipids based on its crystal structure. Embo J 1999; 18: 5166-74.
    CrossrefPubMedGoogle Scholar
  • 22 Panunto-Castelo A, Almeida IC, Rosa JC, Greene LJ, Roque-Barreira MC. The Rubino test for leprosy is a β2-glycoprotein I-dependent antiphospholipid reaction. Immunology 2000; 101: 147-53.
    CrossrefPubMedGoogle Scholar
  • 23 Arvieux J, Darnige L, Hachulla E, Roussel B, Bensa JC, Colomb MG. Species specificity of anti-β2-glycoprotein I autoantibodies and its relevance to anticardiolipin antibody quantitation. Thromb Haemost 1996; 75: 725-30.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Santiago M, Martinelli R, Ko A, Reis EA, Fontes RD, Nascimento EG, Pierangeli S, Espinola R, Gharavi A. Anti-β2 glycoprotein I and anticardiolipin antibodies in leptospirosis, syphilis and Kala-azar. Clin Exp Rheumatol 2001; 19: 425-30.
    PubMedGoogle Scholar
  • 25 Iverson GM, Victoria EJ, Marquis DM. Anti-β2 glycoprotein I (β2GPI) autoantibodies recognize an epitope on the first domain of β2GPI. Proc Natl Acad Sci USA 1998; 95: 15542-6.
    CrossrefPubMedGoogle Scholar
  • 26 Reddel SW, Wang YX, Sheng YH, Krilis SA. Epitope studies with anti-β2GPI-glycoprotein I antibodies from autoantibody and immunized sources. J Autoimmunity 2000; 15: 91-6.
    CrossrefPubMedGoogle Scholar
  • 27 McNeeley PA, Dlott JS, Furie RA, Jack RM, Ortel TL, Triplett DA, Victoria EJ, Linnik MD. β2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of β2-glycoprotein I. Thromb Haemost 2001; 86: 590-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 George J, Gilburd B, Hojnik M, Levy Y, Langevitz P, Matsuura E, Koike T, Shoenfeld Y. Target recognition of β2-glycoprotein I (β2GPI)-dependent anticardiolipin antibodies: evidence for involvement of the fourth domain of β2GPI in antibody binding. J Immunol 1998; 160: 3917-23.
    PubMedGoogle Scholar
  • 29 Bakos L, Correa CC, Bergmann L, Bonamigo RR, Muller LF. Antiphospholipid antibodies thrombotic syndrome misdiagnosed as Lucio’s phenomenon. Int J Lepr Other Mycobact Dis 1996; 64: 320-3.
    PubMedGoogle Scholar
  • 30 Hussain R, Kifayet A, Chiang TJ. Immunoglobulin G1 (IgG1) IgG3 antibodies are markers of progressive disease in leprosy. Infect Immun 1995; 63: 410-5.
    PubMedGoogle Scholar