Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 2001 Sep;54(9):693–698. doi: 10.1136/jcp.54.9.693

Optimising testing for phospholipid antibodies

M Helbert 1, S Bodger 1, J Cavenagh 1, D D'Cruz 1, J Thomas 1, P MacCallum 1
PMCID: PMC1731506  PMID: 11533076

Abstract

Aim—To compare anticardiolipin (ACL) and anti-ß2 glycoprotein 1 (ß2gp1) enzyme linked immunosorbent assays (ELISAs) in the diagnosis of antiphospholipid syndrome (APS) and to incorporate these results into a meta-analysis of published data.

Method—Three representative commercial ACL ELISAs and an in house ß2gp1 assay were optimised and then assessed on 124 sera from normal donors, patients with infection, or patients with APS. A Medline search was screened for papers meeting defined criteria to conduct a meta-analysis. The performance of the assays used in this study was included.

Results—A non-quantitative ACL assay performed at least as well as the anti-ß2gp1 assay in the diagnosis of APS. Meta-analysis confirmed that neither assay is perfect, although the anti-ß2gp1 assay had a higher specificity and lower sensitivity than the ACL assay.

Conclusions—The pooled data suggest that the ACL assay is used to investigate thrombosis without overt underlying pathology and that the improved specificity of the anti-ß2gp1 assay is exploited where infection, connective tissue disease, or atheroma are present.

Key Words: antiphospholipid syndrome • anticardiolipin antibodies • anti-ß2 glycoprotein 1 • sensitivity

Full Text

The Full Text of this article is available as a PDF (192.4 KB).

graphic file with name 00153.f1.jpg

Open in a new tab

Figure 1 Receiver operating characteristic curves for anticardiolipin (ALC) and anti-ß2 glycoprotein 1 (anti-ß2gp1) assays. Assays are: (A) non-quantitative total ACL, (B) quantitative total ACL, (C) IgG ACL, (D) IgM ACL, (E) IgG anti-ß2gp1, (F) IgM anti-ß2gp1.

graphic file with name 00153.f2.jpg

Open in a new tab

Figure 2 Sensitivities (A) and specificities (B) for anticardiolipin (ACL) and anti-ß2 glycoprotein 1 (anti-ß2gp1) assays in individual reports and derived from pooled data.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alarcón-Segovia D., Sanchez-Guerrero J. Primary antiphospholipid syndrome. J Rheumatol. 1989 Apr;16(4):482–488. [PubMed] [Google Scholar]
  2. Arnett F. C., Thiagarajan P., Ahn C., Reveille J. D. Associations of anti-beta2-glycoprotein I autoantibodies with HLA class II alleles in three ethnic groups. Arthritis Rheum. 1999 Feb;42(2):268–274. doi: 10.1002/1529-0131(199902)42:2<268::AID-ANR8>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
  3. Asherson R. A., Cervera R., Piette J. C., Font J., Lie J. T., Burcoglu A., Lim K., Muñoz-Rodríguez F. J., Levy R. A., Boué F. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore) 1998 May;77(3):195–207. doi: 10.1097/00005792-199805000-00005. [DOI] [PubMed] [Google Scholar]
  4. Atsumi T., Tsutsumi A., Amengual O., Khamashta M. A., Hughes G. R., Miyoshi Y., Ichikawa K., Koike T. Correlation between beta2-glycoprotein I valine/leucine247 polymorphism and anti-beta2-glycoprotein I antibodies in patients with primary antiphospholipid syndrome. Rheumatology (Oxford) 1999 Aug;38(8):721–723. doi: 10.1093/rheumatology/38.8.721. [DOI] [PubMed] [Google Scholar]
  5. Balestrieri G., Tincani A., Spatola L., Allegri F., Prati E., Cattaneo R., Valesini G., Del Papa N., Meroni P. Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome? Lupus. 1995 Apr;4(2):122–130. doi: 10.1177/096120339500400208. [DOI] [PubMed] [Google Scholar]
  6. Blanco F. J., Gómez-Reino J. J., de la Mata J., Corrales A., Rodríguez-Valverde V., Rosas J. C., Gómez de la Camara A., Pascual E. Survival analysis of 306 European Spanish patients with systemic lupus erythematosus. Lupus. 1998;7(3):159–163. doi: 10.1191/096120398678919930. [DOI] [PubMed] [Google Scholar]
  7. Chamley L. W., Duncalf A. M., Konarkowska B., Mitchell M. D., Johnson P. M. Conformationally altered beta 2-glycoprotein I is the antigen for anti-cardiolipin autoantibodies. Clin Exp Immunol. 1999 Mar;115(3):571–576. doi: 10.1046/j.1365-2249.1999.00810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chua K. S., Kong K. H. Functional outcome in brain stem stroke patients after rehabilitation. Arch Phys Med Rehabil. 1996 Feb;77(2):194–197. doi: 10.1016/s0003-9993(96)90167-7. [DOI] [PubMed] [Google Scholar]
  9. Day H. M., Thiagarajan P., Ahn C., Reveille J. D., Tinker K. F., Arnett F. C. 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 Apr;25(4):667–674. [PubMed] [Google Scholar]
  10. Galli M., Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome. Blood. 1999 Apr 1;93(7):2149–2157. [PubMed] [Google Scholar]
  11. Guerin J., Feighery C., Sim R. B., Jackson J. Antibodies to beta2-glycoprotein I--a specific marker for the antiphospholipid syndrome. Clin Exp Immunol. 1997 Aug;109(2):304–309. doi: 10.1046/j.1365-2249.1997.4601357.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harris E. N., Pierangeli S. S., Gharavi A. E. Diagnosis of the antiphospholipid syndrome: a proposal for use of laboratory tests. Lupus. 1998;7 (Suppl 2):S144–S148. doi: 10.1177/096120339800700232. [DOI] [PubMed] [Google Scholar]
  13. Irwig L., Tosteson A. N., Gatsonis C., Lau J., Colditz G., Chalmers T. C., Mosteller F. Guidelines for meta-analyses evaluating diagnostic tests. Ann Intern Med. 1994 Apr 15;120(8):667–676. doi: 10.7326/0003-4819-120-8-199404150-00008. [DOI] [PubMed] [Google Scholar]
  14. Khamashta M. A., Cuadrado M. J., Mujic F., Taub N. A., Hunt B. J., Hughes G. R. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. 1995 Apr 13;332(15):993–997. doi: 10.1056/NEJM199504133321504. [DOI] [PubMed] [Google Scholar]
  15. Matsuura E., Igarashi Y., Fujimoto M., Ichikawa K., Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet. 1990 Jul 21;336(8708):177–178. doi: 10.1016/0140-6736(90)91697-9. [DOI] [PubMed] [Google Scholar]
  16. Matsuura E., Igarashi Y., Yasuda T., Triplett D. A., Koike T. Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med. 1994 Feb 1;179(2):457–462. doi: 10.1084/jem.179.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McNally T., Mackie I. J., Isenberg D. A., Machin S. J. beta 2 glycoprotein-I inhibits factor XII activation on triglyceride rich lipoproteins: the effect of antibodies from plasma of patients with antiphospholipid syndrome. Thromb Haemost. 1996 Aug;76(2):220–225. [PubMed] [Google Scholar]
  18. Najmey S. S., Keil L. B., Adib D. Y., DeBari V. A. The association of antibodies to beta 2 glycoprotein I with the antiphospholipid syndrome: a meta-analysis. Ann Clin Lab Sci. 1997 Jan-Feb;27(1):41–46. [PubMed] [Google Scholar]
  19. Nimpf J., Wurm H., Kostner G. M. Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation. Atherosclerosis. 1987 Feb;63(2-3):109–114. doi: 10.1016/0021-9150(87)90110-9. [DOI] [PubMed] [Google Scholar]
  20. Roubey R. A. Immunology of the antiphospholipid antibody syndrome. Arthritis Rheum. 1996 Sep;39(9):1444–1454. doi: 10.1002/art.1780390903. [DOI] [PubMed] [Google Scholar]
  21. Sanmarco M., Soler C., Christides C., Raoult D., Weiller P. J., Gerolami V., Bernard D. 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. 1997 May;129(5):499–506. doi: 10.1016/s0022-2143(97)90004-4. [DOI] [PubMed] [Google Scholar]
  22. Steinbach W. R., Richter K. Multiple classification and receiver operating characteristic (ROC) analysis. Med Decis Making. 1987 Oct-Dec;7(4):234–237. doi: 10.1177/0272989X8700700405. [DOI] [PubMed] [Google Scholar]
  23. Viard J. P., Amoura Z., Bach J. F. Association of anti-beta 2 glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus. Am J Med. 1992 Aug;93(2):181–186. doi: 10.1016/0002-9343(92)90049-h. [DOI] [PubMed] [Google Scholar]
  24. Wilson W. A., Gharavi A. E., Koike T., Lockshin M. D., Branch D. W., Piette J. C., Brey R., Derksen R., Harris E. N., Hughes G. R. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999 Jul;42(7):1309–1311. doi: 10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES