Abstract
Antibodies to β2-glycoprotein I (anti-β2-GPI) have been reported to have stronger association with clinical antiphospholipid syndrome (APS) than anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). We investigated the sensitivity and specificity of ELISA for anti-β2-GPI in Thai systemic lupus erythematosus (SLE) patients with clinical features of APS and compared the results with IgG/IgM aCL and LAC to find the test with the best association. The hospital records of 151 Thai SLE patients whose sera had been sent for either IgG/IgM anticardiolipin antibodies or lupus anticoagulant testing were reviewed. Sera of patients either without complete clinical records or those with APS-related manifestations other than vascular thrombosis and pregnancy morbidity (according to the international consensus statement on preliminary classification criteria for definite APS) were excluded. For the remaining subjects (112 patients), their sera were tested for anti-β2-GPI antibody, IgG and IgM anticardiolipin, and lupus anticoagulant. The sensitivity and specificity of each method were compared by using the chi-square test. Among the 112 (74.2%) SLE patients in the study, 35 (31.3%) presented with preliminary clinical criteria for APS (i.e., vascular thrombosis and pregnancy morbidity) whereas 77 (68.7%) did not. The sensitivity and specificity of anti-β2-GPI determination were 57.1 and 79.2%, respectively, whereas those of IgG aCL were 25.7 and 94.8%, of IgM aCL were 5.7 and 98.7%, and of LAC were 44.8 and 77.3%, respectively. The accuracy of the four tests showed similar association with clinical APS (accuracy of test = 72.3, 73.2, 69.6, and 68.3%, respectively). Concerning the sensitivity, specificity, and difficulty of the methods, the combination of anti-β2-GPI and IgG aCL tests was the best for the diagnosis of APS in Thai SLE patients.
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References
Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 42:1309–1311
Roubey RA (1996) Immunology of the antiphospholipid antibody syndrome. Arthritis Rheum 39:1444–1454
Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RH, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GR (1989) The “primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 68:366–374
Abu-Shakra M, Gladman DD, Urowitz MB, Farewell V (1995) Anticardiolipin antibodies in systemic lupus erythematosus: clinical and laboratory correlations. Am J Med 99:624–628
Wahl DG, Guillemin F, de Maistre E, Perret C, Lecompte T, Thibaut G (1997) Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus—a meta-analysis. Lupus 6:467–473
Lockshin MD, Qamar T, Druzin ML, Goei S (1987) Antibody to cardiolipin, lupus anticoagulant, and fetal death. J Rheumatol 14:259–262
McHugh NJ, Moye DA, James IE, Sampson M, Maddison PJ (1991) Lupus anticoagulant: clinical significance in anticardiolipin positive patients with systemic lupus erythematosus. Ann Rheum Dis 50:548–552
Long AA, Ginsberg JS, Brill-Edwards P, Johnston M, Turner C, Denburg JA, Bensen WG, Cividino A, Andrew M, Hirsh J (1991) The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study. Thromb Haemost 66:520–524
Viard JP, Amoura Z, Bach JF (1992) Association of anti-beta 2 glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus. Am J Med 93:181–186
Cabiedes J, Cabral AR, Alarcon-Segovia D (1995) 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 22:1899–1906
Cabral AR, Cabiedes J, Alarcon-Segovia D (1995) Antibodies to phospholipid-free beta 2-glycoprotein-I in patients with primary antiphospholipid syndrome. J Rheumatol 22:1894–1898
El-Kadi HS, Keil LB, DeBari VA (1995) Analytical and clinical relationships between human IgG autoantibodies to beta 2 glycoprotein I and anticardiolipin antibodies. J Rheumatol 22:2233–2237
Tsutsumi A, Matsuura E, Ichikawa K, Fujisaku A, Mukai M, Kobayashi S, Koike T (1996) Antibodies to beta 2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus. Arthritis Rheum 39:1466–1474
Roubey RA, Maldonado MA, Byrd SN (1996) Comparison of an enzyme-linked immunosorbent assay for antibodies to beta 2-glycoprotein I and a conventional anticardiolipin immunoassay. Arthritis Rheum 39:1606–1607
Cabral AR, Amigo MC, Cabiedes J, Alarcon-Segovia D (1996) 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 101:472–481
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277
Harris EN (1990) Special report. The second international anti-cardiolipin standardization workshop/the Kingston Anti-Phospholipid Antibody Study (KAPS) group. Am J Clin Pathol 94:476–484
Brandt JT, Triplett DA, Alving B, Scharrer I (1995) Criteria for the diagnosis of lupus anticoagulants: an update on behalf of the subcommittee on Lupus anticoagulant/antiphospholipid antibody of the scientific and standardisation committee of the ISTH. Thromb Haemost 74:1185–1190
McNeil HP, Simpson RJ, Chesterman CN, Krilis SA (1990) Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci U S A 87:4120–4124
Roubey RA (1994) Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulants and other “antiphospholipid” autoantibodies. Blood 84:2854–2867
Proctor RR, Rapaprot SI (1961) The partial thromboplastin time with kaolin. A simple screening test for first stage plasma clotting factor deficiency. Am J Clin Pathol 36:212–219
Thiagarajan P, Pengo V, Shapiro SS (1986) The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood 68:869–874
Exner T, Rickard KA, Kronenberg H (1978) A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 40:143–151
Triplett DA, Brandt JT, Kaczor D, Schaeffer J (1983) Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure. Am J Clin Pathol 79:678–682
Schleider MA, Nachman RL, Jaffe EA, Coleman M (1976) A clinical study of the lupus anticoagulant. Blood 48:499–509
Sanmarco M, Soler C, Christides C, Raoult D, Weiller PJ, Gerolami V, Bernard D (1997) Prevalence and clinical significance of IgG isotype anti-beta 2-glycoprotein I antibodies in antiphospholipid syndrome: a comparative study with anticardiolipin antibodies. J Lab Clin Med 129:499–506
Reber G, Arvieux J, Comby E, Degenne D, de Moerloose P, Sanmarco M, Potron G (1995) Multicenter evaluation of nine commercial kits for the quantitation of anticardiolipin antibodies. The Working Group on Methodologies in Haemostasis from the GEHT (Groupe d’Etudes sur l’Hemostase et la Thrombose). Thromb Haemost 73:444–452
Merkel PA, Chang Y, Pierangeli SS, Harris EN, Polisson RP (1999) Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases. J Rheumatol 26:591–596
Balestrieri G, Tincani A, Spatola L, Allegri F, Pratie, Cattaneo R, Valesini G, Del Papa N, Meroni (1995) Anti-beta 2-glycoprotein I antibodies: a marker of antiphospolid syndrom? Lupus 4:122–130
Franklin RD, Hollier N, Kutteh WH (2000) β2-Glycoprotein 1 as a marker of antiphospholipid syndrome in women with recurrent pregnancy loss. Fertil Steril 73:531–535
Tubach F, Hayem G, Marchand JL, Weber M, Palazzo E, de Bandt M, Roux S, Kahn MF, Meyer O (2000) IgG anti-beta2-glycoprotein I antibodies in adult patients with systemic lupus erythematosus: prevalence and diagnostic value for the antiphospholipid syndrome. J Rheumatol 27:1437–1443
Matsuda J, Saitoh N, Gotoh M, Gohchi K, Tsukamoto M (1995) Prevalence of beta 2-glycoprotein I antibody in systemic lupus erythematosus patients with beta 2-glycoprotein I dependent antiphospholipid antibodies. Ann Rheum Dis 54:73–75
Day HM, Thiagarajan P, Ahn C, Reveille JD, Tinker KF, Arnett FC (1998) 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 25:667–674
Fanopoulos D, Teodorescu MR, Varga J, Teodorescu M (1998) High frequency of abnormal levels of IgA anti-beta2-glycoprotein I antibodies in patients with systemic lupus erythematosus: relationship with antiphospholipid syndrome. J Rheumatol 25:675–680
Sanfilippo SS, Khamashta MA, Atsumi T, Amengual O, Bertolaccini ML, D’Cruz D, Amft N, Swana GT, Hughes GR (1998) Antibodies to beta2-glycoprotein I: a potential marker for clinical features of antiphospholipid antibody syndrome in patients with systemic lupus erythematosus. J Rheumatol 25:2131–2134
Bruce IN, Clark-Soloninka CA, Spitzer KA, Gladman DD, Urowitz MB, Laskin CA (2000) 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 27:2833–2837
Lee SS, Cho ML, Joo YS, Kim WU, Hong YS, Min JK, Lee SH, Park SH, Cho CS, Kim HY (2001) Isotypes of anti-beta2-glycoprotein I antibodies: association with thrombosis in patients with systemic lupus erythematosus. J Rheumatol 28:520–524
Voss A, Jacobsen S, Heegaard NH (2001) Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia. Lupus 10:533–538
von Scheven E, Glidden DV, Elder ME (2002) Anti-beta2-glycoprotein I antibodies in pediatric systemic lupus erythematosus and antiphospholipid syndrome. Arthritis Rheum 47:414–420
Acknowledgment
We are grateful to Ms. Umaporn Udomsubpayakul for her help on this statistical analysis. This study was supported by a research grant from the Faculty of Medicine, Ramathibodi Hospital, Mahidol University, no. 14/2003.
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Parkpian, V., Verasertniyom, O., Vanichapuntu, M. et al. Specificity and sensitivity of anti-β2-glycoprotein I as compared with anticardiolipin antibody and lupus anticoagulant in Thai systemic lupus erythematosus patients with clinical features of antiphospholipid syndrome. Clin Rheumatol 26, 1663–1670 (2007). https://doi.org/10.1007/s10067-007-0566-5
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DOI: https://doi.org/10.1007/s10067-007-0566-5