Subscribe to RSS
DOI: 10.1160/TH04-04-0230
Heterogeneity of anti-β2-glycoprotein I antibodies
A factor of variability in test resultsCorrespondence to:
Publication History
Received
14 April 2004
Accepted after revision
14 September 2004
Publication Date:
14 December 2017 (online)
Summary
The aim of this study was to evaluate the heterogeneity of IgG-anti- β2 -glycoprotein I antibodies (IgG-aβ2 GPI) as regarding their reactivity pattern against different sources of human β2 GPI,their avidity and their association with clinical events of antiphospholipid syndrome (APS).Three thousand six hundred and eightyfour consecutive patient sera were routinely tested for IgG-a β2 GPI over 1 year using an in-house ELISA with 2 different commercial preparations of human purified β2GPI. Of the 340 sera found positive, all those clinically documented were included in this study; 61 were positive with only one preparation (S1) and 59 with both (S2).The results of ELISA were confirmed by Western blot. Heterogeneity was stressed by testing sera with a human recombinant protein and 3 β2 GPI-related peptides. No contribution of glycosylation in the binding to β2GPI was found.The avidity indices for each protein were significantly higher in S1 than in S2 (p = 0.0021). S2 were more associated with antiphospholipid antibodies than S1 (75% versus 21% ; p <0.0001).A similar frequency of the main clinical features of APS was found in S1 and S2 sera (69% and 71%, respectively). In conclusion, our data show a heterogeneity in the antigenic reactivity pattern of IgG- a β2 GPI and a relationship between a binding profile and antibody avidity.This heterogeneity could represent a crucial factor of variability in test results and underlines the difficulty of getting standardisation.
#
#
-
References
- 1 Najmey SS, Keil LB, Adib DY. et al The association of antibodies to beta 2 glycoprotein I with the antiphospholipid syndrome: a meta-analysis. Ann Clin Lab Sci 1997; 27: 41-6.
- 2 Wilson WA, Gharavi AE, Koike T. et al International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309-11.
- 3 Asherson RA, Khamashta MA, Ordi-Ros J. et al The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore). 1989; 68: 366-74.
- 4 Alarcon-Segovia D, Deleze M, Oria CV. et al Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore). 1989; 68: 353-65.
- 5 Reber G, Schousboe I, Tincani A. et al Inter-laboratory variability of anti-beta2-glycoprotein I measurement. A collaborative study in the frame of the European Forum on Antiphospholipid Antibodies Standardization Group. Thromb Haemost 2002; 88: 66-73.
- 6 Lozier J, Takahashi N, Putnam FW. Complete amino acid sequence of human plasma beta 2-glycoprotein I. Proc Natl Acad Sci USA 1984; 81: 3640-4.
- 7 Bouma B, de Groot PG, van den Elsen JM. et al Adhesion mechanism of human beta(2)-glycoprotein I to phospholipids based on its crystal structure. EMBO J 1999; 18: 5166-74.
- 8 Schwarzenbacher R, Zeth K, Diederichs K. et al Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome. EMBO J 1999; 18: 6228-39.
- 9 Hunt JE, Simpson RJ, Krilis SA. Identification of a region of beta 2-glycoprotein I critical for lipid binding and anti-cardiolipin antibody cofactor activity. Proc Natl Acad Sci USA 1993; 90: 2141-5.
- 10 Roubey RA, Eisenberg RA, Harper MF. et al "Anticardiolipin" autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding. J Immunol 1995; 154: 954-60.
- 11 Tincani A, Spatola L, Prati E. et al The antibeta2- glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2-glycoprotein I and preserved during species’ evolution. J Immunol 1996; 157: 5732-8.
- 12 Matsuura E, Igarashi Y, Yasuda T. et al Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179: 457-62.
- 13 Iverson GM, Victoria EJ, Marquis DM. Anti-beta2 glycoprotein I (beta2GPI) autoantibodies recognize an epitope on the first domain of beta2GPI. Proc Natl Acad Sci USA 1998; 95: 15542-6.
- 14 McNeeley PA, Dlott JS, Furie RA. et al Beta2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of beta2-glycoprotein I. Thromb Haemost 2001; 86: 590-5.
- 15 Igarashi M, Matsuura E, Igarashi Y. et al Human beta2-glycoprotein I as an anticardio-lipin cofactor determined using mutants expressed by a baculovirus system. Blood 1996; 87: 3262-70.
- 16 Koike T, Ichikawa K, Atsumi T. et al Beta 2-glycoprotein I-anti-beta 2-glycoprotein I interaction. J Autoimmun 2000; 15: 97-100.
- 17 Blank M, Shoenfeld Y, Cabilly S. et al Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides. Proc Natl Acad Sci USA 1999; 96: 5164-8.
- 18 Verrot D, SanMarco M, Dravet C. et al Prevalence and signification of antinuclear and anticardiolipin antibodies in patients with epilepsy. Am J Med 1997; 103: 33-7.
- 19 Vlachoyiannopoulos PG, Petrovas C, Tektonidou M. et al Antibodies to B2-GPI: Urea resistance, binding , specificity and association with thrombosis. J Clin Immunol 1998; 18: 380-91.
- 20 Cabral AR, Amigo MC, Cabiedes J. et al The antiphospholipid/cofactor syndromes: a primary variant with antibodies to beta 2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays. Am J Med 1996; 101: 472-81.
- 21 Shoenfeld Y, Krause I, Kvapil F. et al Prevalence and clinical correlations of antibodies against six β 2-glycoprotein I-related peptides in the antiphospholipid syndrome. J Clin Immunol 2003; 23: 375-81.
- 22 Schousboe I. Characterization of subfractions of beta 2-glycoprotein I: evidence for sialic acid microheterogeneity. Int J Biochem 1983; 15: 35-44.
- 23 Gries A, Nimpf J, Wurm H. et al Characterization of isoelectric subspecies of asialo-beta 2-glycoprotein I. Biochem J 1989; 260: 531-4.
- 24 Brighton TA, Dai YP, Hogg PJ. et al Microheterogeneity of beta-2 glycoprotein I: implications for binding to anionic phospholipids. Biochem J 1999; 340: 59-67.
- 25 Arvieux J, Roussel B, Ponard D. et al IgG2 subclass restriction of anti-b2 glycoprotein 1 antibodies in autoimmune patients. Clin Exp Immunol 1994; 95: 310-5.
- 26 Zanon E, Prandoni P, Vianello F. et al Antibeta2- glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism. Thromb Res 1999; 96: 269-74.
- 27 Cabiedes J, Cabral AR, Alarcon-Segovia D. Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-beta 2-glycoprotein-I than with antiphospholipid antibodies. J Rheumatol 1995; 22: 1899-906.
- 28 Bruce IN, Clark-Soloninka CA, Spitzer KA. et al Prevalence of antibodies to beta2-glycoprotein I in systemic lupus erythematosus and their association with antiphospholipid antibody syndrome criteria : a single center study and literature review. J Rheumatol 2000; 27: 2833-7.
- 29 Day HM, Thiagarajan P, Ahn C. et al Autoantibodies to beta2-glycoprotein I in systemic lupus erythematosus and primary antiphospholipid antibody syndrome: clinical correlations in comparison with other antiphospholipid antibody tests. J Rheumatol 1998; 25: 667-74.
- 30 Forastiero RR, Martinuzzo ME, Carreras LO. Binding properties of antibodies to prothrombin and beta2-glycoprotein I (beta2-GPI) assayed by ELISA and dot blot. Clin Exp Immunol 1999; 118: 480-6.
- 31 Previtali S, Barbui T, Galli M. Anti-beta2-glycoprotein I and anti-prothrombin antibodies in antiphospholipid- negative patients with thrombosis: a case control study. Thromb Haemost 2002; 88: 729-32.
- 32 Galli M, Luciani D, Bertolini G. et al Antibeta2- glycoprotein I, antiprothrombin antibodies and the risk of thrombosis in the antiphospholipid syndrome. Blood 2003; 102: 2717-23.
- 33 Lynch A, Byers T, Emlen W. et al Association of antibodies to beta2-Glycoprotein 1 with pregnancy loss and pregnancy-induced hypertension : a prospective study in low-risk pregnancy. Obstet Gynecol 1999; 93: 193-8.
- 34 Franklin RD, Hollier N, Kutteh WH. Beta2-Glycoprotein 1 as a marker of antiphospholipid syndrome in women with recurrent pregnancy loss. Fertil Steril 2000; 73: 531-5.
- 35 Gris JC, Quere I, Sanmarco M. et al Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nimes Obstetricians and Haematologists Study-NOHA. Thromb Haemost 2000; 84: 228-36.
Correspondence to:
-
References
- 1 Najmey SS, Keil LB, Adib DY. et al The association of antibodies to beta 2 glycoprotein I with the antiphospholipid syndrome: a meta-analysis. Ann Clin Lab Sci 1997; 27: 41-6.
- 2 Wilson WA, Gharavi AE, Koike T. et al International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309-11.
- 3 Asherson RA, Khamashta MA, Ordi-Ros J. et al The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore). 1989; 68: 366-74.
- 4 Alarcon-Segovia D, Deleze M, Oria CV. et al Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore). 1989; 68: 353-65.
- 5 Reber G, Schousboe I, Tincani A. et al Inter-laboratory variability of anti-beta2-glycoprotein I measurement. A collaborative study in the frame of the European Forum on Antiphospholipid Antibodies Standardization Group. Thromb Haemost 2002; 88: 66-73.
- 6 Lozier J, Takahashi N, Putnam FW. Complete amino acid sequence of human plasma beta 2-glycoprotein I. Proc Natl Acad Sci USA 1984; 81: 3640-4.
- 7 Bouma B, de Groot PG, van den Elsen JM. et al Adhesion mechanism of human beta(2)-glycoprotein I to phospholipids based on its crystal structure. EMBO J 1999; 18: 5166-74.
- 8 Schwarzenbacher R, Zeth K, Diederichs K. et al Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome. EMBO J 1999; 18: 6228-39.
- 9 Hunt JE, Simpson RJ, Krilis SA. Identification of a region of beta 2-glycoprotein I critical for lipid binding and anti-cardiolipin antibody cofactor activity. Proc Natl Acad Sci USA 1993; 90: 2141-5.
- 10 Roubey RA, Eisenberg RA, Harper MF. et al "Anticardiolipin" autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding. J Immunol 1995; 154: 954-60.
- 11 Tincani A, Spatola L, Prati E. et al The antibeta2- glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2-glycoprotein I and preserved during species’ evolution. J Immunol 1996; 157: 5732-8.
- 12 Matsuura E, Igarashi Y, Yasuda T. et al Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179: 457-62.
- 13 Iverson GM, Victoria EJ, Marquis DM. Anti-beta2 glycoprotein I (beta2GPI) autoantibodies recognize an epitope on the first domain of beta2GPI. Proc Natl Acad Sci USA 1998; 95: 15542-6.
- 14 McNeeley PA, Dlott JS, Furie RA. et al Beta2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of beta2-glycoprotein I. Thromb Haemost 2001; 86: 590-5.
- 15 Igarashi M, Matsuura E, Igarashi Y. et al Human beta2-glycoprotein I as an anticardio-lipin cofactor determined using mutants expressed by a baculovirus system. Blood 1996; 87: 3262-70.
- 16 Koike T, Ichikawa K, Atsumi T. et al Beta 2-glycoprotein I-anti-beta 2-glycoprotein I interaction. J Autoimmun 2000; 15: 97-100.
- 17 Blank M, Shoenfeld Y, Cabilly S. et al Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides. Proc Natl Acad Sci USA 1999; 96: 5164-8.
- 18 Verrot D, SanMarco M, Dravet C. et al Prevalence and signification of antinuclear and anticardiolipin antibodies in patients with epilepsy. Am J Med 1997; 103: 33-7.
- 19 Vlachoyiannopoulos PG, Petrovas C, Tektonidou M. et al Antibodies to B2-GPI: Urea resistance, binding , specificity and association with thrombosis. J Clin Immunol 1998; 18: 380-91.
- 20 Cabral AR, Amigo MC, Cabiedes J. et al The antiphospholipid/cofactor syndromes: a primary variant with antibodies to beta 2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays. Am J Med 1996; 101: 472-81.
- 21 Shoenfeld Y, Krause I, Kvapil F. et al Prevalence and clinical correlations of antibodies against six β 2-glycoprotein I-related peptides in the antiphospholipid syndrome. J Clin Immunol 2003; 23: 375-81.
- 22 Schousboe I. Characterization of subfractions of beta 2-glycoprotein I: evidence for sialic acid microheterogeneity. Int J Biochem 1983; 15: 35-44.
- 23 Gries A, Nimpf J, Wurm H. et al Characterization of isoelectric subspecies of asialo-beta 2-glycoprotein I. Biochem J 1989; 260: 531-4.
- 24 Brighton TA, Dai YP, Hogg PJ. et al Microheterogeneity of beta-2 glycoprotein I: implications for binding to anionic phospholipids. Biochem J 1999; 340: 59-67.
- 25 Arvieux J, Roussel B, Ponard D. et al IgG2 subclass restriction of anti-b2 glycoprotein 1 antibodies in autoimmune patients. Clin Exp Immunol 1994; 95: 310-5.
- 26 Zanon E, Prandoni P, Vianello F. et al Antibeta2- glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism. Thromb Res 1999; 96: 269-74.
- 27 Cabiedes J, Cabral AR, Alarcon-Segovia D. Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-beta 2-glycoprotein-I than with antiphospholipid antibodies. J Rheumatol 1995; 22: 1899-906.
- 28 Bruce IN, Clark-Soloninka CA, Spitzer KA. et al Prevalence of antibodies to beta2-glycoprotein I in systemic lupus erythematosus and their association with antiphospholipid antibody syndrome criteria : a single center study and literature review. J Rheumatol 2000; 27: 2833-7.
- 29 Day HM, Thiagarajan P, Ahn C. et al Autoantibodies to beta2-glycoprotein I in systemic lupus erythematosus and primary antiphospholipid antibody syndrome: clinical correlations in comparison with other antiphospholipid antibody tests. J Rheumatol 1998; 25: 667-74.
- 30 Forastiero RR, Martinuzzo ME, Carreras LO. Binding properties of antibodies to prothrombin and beta2-glycoprotein I (beta2-GPI) assayed by ELISA and dot blot. Clin Exp Immunol 1999; 118: 480-6.
- 31 Previtali S, Barbui T, Galli M. Anti-beta2-glycoprotein I and anti-prothrombin antibodies in antiphospholipid- negative patients with thrombosis: a case control study. Thromb Haemost 2002; 88: 729-32.
- 32 Galli M, Luciani D, Bertolini G. et al Antibeta2- glycoprotein I, antiprothrombin antibodies and the risk of thrombosis in the antiphospholipid syndrome. Blood 2003; 102: 2717-23.
- 33 Lynch A, Byers T, Emlen W. et al Association of antibodies to beta2-Glycoprotein 1 with pregnancy loss and pregnancy-induced hypertension : a prospective study in low-risk pregnancy. Obstet Gynecol 1999; 93: 193-8.
- 34 Franklin RD, Hollier N, Kutteh WH. Beta2-Glycoprotein 1 as a marker of antiphospholipid syndrome in women with recurrent pregnancy loss. Fertil Steril 2000; 73: 531-5.
- 35 Gris JC, Quere I, Sanmarco M. et al Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nimes Obstetricians and Haematologists Study-NOHA. Thromb Haemost 2000; 84: 228-36.