Skip to main content
SpringerLink
Log in

Classical and additional antiphospholipid antibodies in blood samples of ischemic stroke patients and healthy controls

  • Novel Aspects in Lupus, 2017
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Classical antiphospholipid antibodies (aPLa) are found in 6–25% of blood samples from stroke patients. The frequency of novel aPLa antibodies in blood samples of CVA patients is not known. Enzyme-linked immunosorbent assays (ELISA) were performed on blood samples from 209 CVA patients (170 samples were obtained during the acute phase and 39 samples were from patients with complete carotid stenosis) and compared to 54 healthy controls. Subjects were tested for the presence of the classical aPL antibodies anticardiolipin (aCL) and anti-beta2-glycoprotein (aβ2gI), in addition to antiphosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and Annexin V. All antibodies were tested for both IgM and IgG subclasses. Numeric analysis of the antibody titer levels (μ/ml) revealed a significantly higher subclinical titer by two standard deviations of many aPL autoantibodies among CVA patients (Pv < 0.05). However, according to the kit manufacturer’s cutoff value, no positive antibodies were found except a trend toward higher percentage of positive aPS IgG titer in the CVA group compared to controls (6.2 vs. %0; P = 0.077). According to the manufacturer’s cutoff, significantly higher levels of positive antibodies were not found among stroke patients. However, the absolute ELISA values of stroke patients were significantly higher. These results suggest that lower cutoff values than those used for APS diagnosis should be used for risk stratification of CVA among healthy individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Jankowski M, Vreys I, Wittevrongel C, Boon D, Vermylen J, Hoylaerts MF, et al. Thrombogenicity of beta 2-glycoprotein I-dependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood. 2003;101:157–62.

    Article  CAS  PubMed  Google Scholar 

  2. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.

    Article  CAS  PubMed  Google Scholar 

  3. Sugi T, Matsubayashi H, Inomo A, Dan L, Makino T. Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid-to-late pregnancy loss. J Obstet Gynaecol Res. 2004;30(4):326–32.

    Article  PubMed  Google Scholar 

  4. Tebo AE, Jaskowski TD, Hill HR, Branch DW. Clinical relevance of multiple antibody specificity testing in anti-phospholipid syndrome and recurrent pregnancy loss. Clin Exp Immunol. 2008;154(3):332–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Krnic-Barrie S, O’Connor CR, Looney SW, Pierangeli SS, Harris EN. A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis. Arch Intern Med. 1997;157(18):2101–8.

    Article  CAS  PubMed  Google Scholar 

  6. Shah NM, Khamashta MA, Atsumi T, Hughes GRV. Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients. Lupus. 1998;7(1):3–6.

    Article  CAS  PubMed  Google Scholar 

  7. Cervera R, Piette J-C, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019–27.

    Article  PubMed  Google Scholar 

  8. Dobrynina LA, Kalashnikova LA, Pavlova LN. [Ischemic stroke in young age]. Zhurnal Nevrol Psikhiatrii Im SS Korsakova Minist Zdr Meditsinskoĭ Promyshlennosti Ross Fed Vserossiĭskoe Obshchestvo Nevrol Vserossiĭskoe Obshchestvo Psikhiatrov. 2011; 111 (3):4–8.

  9. Erkan D, Merrill JT, Yazici Y, Sammaritano L, Buyon JP, Lockshin MD. High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum. 2001;44(6):1466–7.

    Article  CAS  PubMed  Google Scholar 

  10. Dragoni F, Chiarotti F, Rosano G, Simioni P, Tormene D, Mazzucconi MG, et al. Thrombophilic screening in young patients (<40 years) with idiopathic ischemic stroke: a controlled study. Thromb Res. 2011;127(2):85–90.

    Article  CAS  PubMed  Google Scholar 

  11. Ferro JM. Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and dural sinus thrombosis (ISCVT). Stroke. 2004;35(3):664–70.

    Article  PubMed  Google Scholar 

  12. Cantu C, Alonso E, Jara A, Martínez L, Ríos C, Fernández M, de los A, et al. Hyperhomocysteinemia, low folate and vitamin B12 concentrations, and methylene tetrahydrofolate reductase mutation in cerebral venous thrombosis. Stroke J Cereb Circ. 2004;35(8):1790–1794.

  13. Koniari I, Siminelakis SN, Baikoussis NG, Papadopoulos G, Goudevenos J, Apostolakis E. Antiphospholipid syndrome; its implication in cardiovascular diseases: a review. J Cardiothorac Surg. 2010;5:101.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. The Antiphospholipid Antibodies in Stroke Study (APASS) Group. Neurology. 1993; 43(10):2069–73.

  15. Investigators A. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA J Am Med Assoc. 2004;291(5):576–84.

    Article  Google Scholar 

  16. Brey RL, Abbott RD, Curb JD, Sharp DS, Ross GW, Stallworth CL, et al. 2-glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the Honolulu heart program. Stroke. 2001;32(8):1701–6.

    Article  CAS  PubMed  Google Scholar 

  17. Brey RL, Stallworth CL, McGlasson DL, Wozniak MA, Wityk RJ, Stern BJ, et al. Antiphospholipid antibodies and stroke in young women. Stroke J Cereb Circ. 2002;33(10):2396–400.

    Article  CAS  Google Scholar 

  18. Piette JC. Towards improved criteria for the antiphospholipid syndrome. Lupus. 1998;7(Suppl 2):S149–57.

    Article  PubMed  Google Scholar 

  19. Okuma H, Kitagawa Y, Takagi S. Investigation of antiphosphatidyl-serine antibody and antiphosphatidyl-inositol antibody in ischemic stroke patients. Clin Dev Immunol. 2010;2010:1–4.

    Article  Google Scholar 

  20. Toschi V, Motta A, Castelli C, Paracchini ML, Zerbi D, Gibelli A. High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause. Stroke J Cereb Circ. 1998;29(9):1759–64.

    Article  CAS  Google Scholar 

  21. Tuhrim S, Rand JH, Wu X, Horowitz DR, Weinberger J, Goldman ME, et al. Antiphosphatidyl serine antibodies are independently associated with ischemic stroke. Neurology. 1999;53(7):1523–7.

    Article  CAS  PubMed  Google Scholar 

  22. Okuma H, Kitagawa Y, Kobori S, Sekiyama S, Takagi S. Prevalence rates of antiphospholipid antibodies in ischemic stroke patients. Intern Med Tokyo Jpn. 2006;45(17):1017–8.

    Article  Google Scholar 

  23. Okuma H, Kitagawa Y, Ishikawa T, Takagi S. Study of phosphatidylserine-dependent anti-prothrombin antibody in cerebral infarction. Intern Med Tokyo Jpn. 2009;48(16):1351–5.

    Article  Google Scholar 

  24. Lee KO, Kim WJ, Na S-J, Heo JH, Lee K-Y. Clinical significance of anti-annexin V antibody in acute cerebral ischemia. J Neurol Sci. 2011;305(1–2):53–6.

    Article  CAS  PubMed  Google Scholar 

  25. Hughes GRV, Khamashta MA. Seronegative antiphospholipid syndrome. Ann Rheum Dis. 2003;62(12):1127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tripodi A, de Groot PG, Pengo V. Antiphospholipid syndrome: laboratory detection, mechanisms of action and treatment: review: antiphospholipid syndrome. J Intern Med. 2011;270(2):110–22.

    Article  CAS  PubMed  Google Scholar 

  27. Pengo V, Biasiolo A, Bison E, Chantarangkul V, Tripodi A. Italian Federation of Anticoagulation Clinics (FCSA). Antiphospholipid antibody ELISAs: survey on the performance of clinical laboratories assessed by using lyophilized affinity-purified IgG with anticardiolipin and anti-beta2-glycoprotein I activity. Thromb Res. 2007;120(1):127–33.

    Article  CAS  PubMed  Google Scholar 

  28. Yasuda S, Bohgaki M, Atsumi T, Koike T. Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway. Immunobiology. 2005;210(10):775–80.

    Article  CAS  PubMed  Google Scholar 

  29. Castillo J, Leira R. Predictors of deteriorating cerebral infarct: role of inflammatory mechanisms. Would its early treatment be useful? Cerebrovasc Dis Basel Switz. 2001;11(Suppl 1):40–8.

    Google Scholar 

  30. Vila N, Filella X, Deulofeu R, Ascaso C, Abellana R, Chamorro A. Cytokine-induced inflammation and long-term stroke functional outcome. J Neurol Sci. 1999;162(2):185–8.

    Article  CAS  PubMed  Google Scholar 

  31. Waje-Andreassen U, Krakenes J, Ulvestad E, Thomassen L, Myhr K-M, Aarseth J, et al. IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurol Scand. 2005;111(6):360–5.

    Article  CAS  PubMed  Google Scholar 

  32. Orion D, Schwammenthal Y, Reshef T, Schwartz R, Tsabari R, Merzeliak O, et al. Interleukin-6 and soluble intercellular adhesion molecule-1 in acute brain ischaemia. Eur J Neurol Off J Eur Fed Neurol Soc. 2008;15(4):323–8.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Narin-Nard Carmel-Neiderman

  2. Department of Medicine E, Meir Medical Center, Kfar Saba, Israel

    Narin-Nard Carmel-Neiderman, Pnina Rotman-Pikielny & Yair Levy

  3. Joseph Sagol Neuroscience Center (JSNC), Sheba Medical Center, Ramat Gan, Israel

    David Tanne & Idan Goren

Authors
  1. Narin-Nard Carmel-Neiderman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Tanne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Idan Goren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pnina Rotman-Pikielny
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yair Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yair Levy.

Ethics declarations

Conflict of interests

The authors declare that they have no conflict of interest.

Disclosure

None.

Funding

The study was not funded.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carmel-Neiderman, NN., Tanne, D., Goren, I. et al. Classical and additional antiphospholipid antibodies in blood samples of ischemic stroke patients and healthy controls. Immunol Res 65, 470–476 (2017). https://doi.org/10.1007/s12026-017-8897-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-017-8897-z

Keywords

Search

Navigation