Skip to main content
SpringerLink
Log in

Oxidativ modifizierte Lipoproteine und deren Antikörper bei Patienten mit Antiphospholipidsyndrom und Systemischem Lupus erythematodes

Oxidatively modified lipoproteins and their antibodies in patients with antiphospholipid syndromeand systemic lupus erythematosus

  • ORIGINALARBEIT
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung.

Das Antiphospholipidsyndrom (APS), mit den typischen klinischen Manifestationen von rezidivierenden Thrombosen und Aborten, wird laborchemisch durch das Vorkommen von Antiphospholipidantikörpern (aPL) definiert. Das Krankheitsbild gewinnt in letzter Zeit als mögliches Bindeglied zwischen Autoimmunität und Atherosklerose zunehmend an Bedeutung. Sowohl aPL, als auch oxidierten low-density Lipoproteinen (oxLDL) und deren Antikörpern (Anti-oxLDL) wird eine pathogenetische Bedeutung in der Atherogenese zugesprochen. In unserer Studie verglichen wir die Serumspiegel von oxLDL und AntioxLDL bei APS-Patienten (20 Patienten primäres/14 sekundäres APS) und nonAPS-Patienten (24 phänotypisch gesunde Kontrollpersonen und 12 Patienten mit Systemischem Lupus erythematodes/ SLE/) und untersuchten Assoziationen dieser Parameter zur Intima-Media-Dicke (IMT), einem klinischen Surrogatparameter der Atherosklerose.

SLE-Patienten mit und ohne APS wiesen signifikant erhöhte Anti-oxLDL-Spiegel im Vergleich zur Kontrollgruppe auf (p = 0,038 bzw. p = 0,007). Dahingegen unterschieden sich die oxLDL-Konzentrationen nicht signifikant bei Kontrollen und Patienten. DieAntioxLDL- Spiegel korrelierten signifikant mit Anticardiolipin- (p = 0,002) und β 2-Glykoprotein-IAntikörpern (p < 0,048), jeweils vomIgG-Isotyp. Nur SLE-Patienten ohne APS wiesen eine signifikant erhöhte Produktion reaktiver Sauerstoffspezies (ROS) als Zeichen eines proatherogenen oxidativen Stresses in der Zirkulation auf (p < 0,002). Sowohl die zirkulierenden oxLDL- als auch die AntioxLDL- Spiegel wiesen keine Assoziation zur Atherosklerose, gemessen an der IMT, bei den Patientengruppen auf. Zusammenfassend ergibt sich aus unseren experimentellen Daten kein Hinweis darauf, dass bei APS-Patienten eine durch oxidativen Stress beschleunigte Atherosklerose auftritt.

Summary.

The antiphospholipid syndrome (APS) with its typical clinical manifestations of recurrent thrombosis and fetal loss is biochemically defined by the presence of circulating antiphospholipid antibodies (aPL). The disease pattern has raised special interest as a possible link between autoimmunity and atherosclerosis. aPL, oxidized low density lipoproteins (oxLDL), and antibodies to oxLDL (Anti-oxLDL) are suggested to play an important role in atherogenesis. In the present study we compared the serum levels of oxLDL and Anti-oxLDL in APS patients (20 subjects with primary APS; 14 subjects with secondary APS) and nonAPS subjects (24 phenotypically healthy controls samples and 12 patients with systemic lupus erythematosus [SLE]) and investigated associations of the above mentioned parameters with the intima-media thickness (IMT), a clinical surrogate parameter of atherosclerosis.

SLE patients with and without APS showed significantly increased levels of Anti-oxLDL as compared to the controls group (p = 0.038 and p = 0.007, respectively). In contrast, oxLDL levels were not significantly different between the controls group and patients. The Anti-oxLDL levels correlated significantly with anticardiolipin (p = 0.002) and β 2-glycoprotein I antibodies (p < 0.048), both from IgG isotype. Only SLE patients without APS revealed a significantly elevated production of reactive oxygen species indicating an increased proatherogenic oxidative stress in the circulation (p < 0.002). In the patient groups, the circulating levels of oxLDL and Anti-oxLDL showed no association with atherosclerosis as estimated by IMT. In conclusion, our experimental data do not support the concept of oxidative stress-induced accelerated atherosclerosis in APS patients.

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.

References

  1. Allen RC, Dale DC, Taylor FB (2000) Blood phagocyte luminescence: gauging systemic immune activation. Methods Enzymol 305:591–629

    Article  CAS  PubMed  Google Scholar 

  2. Amengual O, Atsumi T, Khamashta MA, Tinahones F, Hughes GRV (1997) Autoantibodies against oxidized low-density lipoprotein in antiphospholipid syndrome. Br J Rheumatol 36:964–968

    Article  CAS  PubMed  Google Scholar 

  3. Asherson RA, Mackay JR, Harris EN (1986) Myocardial infarction in a young man with systemic lupus erythematosus, deep vein thrombosis, and antibodies to phospholipids. Br Heart J 56:190–193

    CAS  PubMed  Google Scholar 

  4. Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications. Diabetes 48:1–9

    CAS  PubMed  Google Scholar 

  5. Berliner JA, Heinecke JW (1996) The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 20:707–727

    Article  CAS  PubMed  Google Scholar 

  6. Chisholm GM, Steinberg D (2000) The oxidative modification hypothesis of atherogenesis: an overview. Free Rad Biol Med 28:1815–1826

    Article  PubMed  Google Scholar 

  7. Cuadrado MJ, Tinahones F, Camps MT, de Ramon E, Gomez-Zumaquero JM, Mujic et al (1998) Antiphospholipid, anti-beta 2-glycoprotein I and anti-oxidized-low-density antibodies in antiphospholipid syndrome. Quart J Med 91:619–626

    Article  CAS  Google Scholar 

  8. Haberland ME, Olch CL, Fogelman AM (1984) Role of lysines in mediating interactionof modified low-densitiy lipoprotein with the scavenger receptor of human monocyte makrophages. J Biol Chem 259:11305–11311

    CAS  PubMed  Google Scholar 

  9. Halliwell B, Chisholm GM, Steinberg D (2000) The oxidative modification hypothesis of atherogenesis: an overview. Free Rad Biol Med 28:1815–1826

    Article  PubMed  Google Scholar 

  10. Hasunuma Y, Matsuura E, Makita Z (1997) Involvement of β 2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages. Clin Exp Immunol 107:569

    Article  CAS  PubMed  Google Scholar 

  11. Hayem G, Nicaise-Roland P, Palazzo E, de Bandt M, Tubach F, Weber M, Meyer O (2001) Anti-oxidized low density lipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome. Lupus 10:346–341

    Article  CAS  PubMed  Google Scholar 

  12. Holvoet P, Stassen JM, Van Cleemput J, Collen D, Vanhaecke J (1998) Oxidized low density lipoprotein in patients with transplant-associated coronary artery disease. Arterioscler Thromb Vasc Biol 18:100–107

    CAS  PubMed  Google Scholar 

  13. Hörkko S, Miller E, Dudl E, Reaven P, Curtiss LK, Zvaifler NJ, Terkeltaub R, Pierangeli SS, Branch DW, Palinski W, Witztum JL (1996) Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. J Clin Invest 98:815–825

    PubMed  Google Scholar 

  14. Hughes GRV (2000) Immunology, lupus and atheroma. Lupus 9:159–160

    Article  CAS  PubMed  Google Scholar 

  15. Kopprasch S, Graessler J, Kohl M, Bergmann S, Schröder HE (1996) Comparison of circulating phagocyte oxidative activity measured by chemiluminescence in whole blood and isolated polymorphonuclear leukocytes. Clin Chim Acta 253:145–157

    Article  CAS  PubMed  Google Scholar 

  16. Lahita RG (2000) Antiphospholipid antibodies as a risk factor for atherosclerosis. In: Hughes Syndrome: Antiphospholipid Syndrome. Khamashta MA, Springer, London Berlin Heidelberg, pp 167–171

  17. Maaravi Y, Raz E, Gilon D, Rubinow A (1989) Cerebrovascular accident and myocardial infarction associated with anticardiolipin antibodies in a young woman with systemic lupus erythematosus. Ann Rheum Dis 48:853–855

    CAS  PubMed  Google Scholar 

  18. Matsuura E, Katahira T, Igarashi Y, Koike T (1994) β 2-glycoprotein I bound to oxidatively modified lipoproteins could be targeted by anticardiolipin antibodies. Lupus 3:314

    Google Scholar 

  19. Metsä-Ketelä T (1991) Luminescent assay for total peroxyl radical-trapping capability of plasma. In: Stanley P, Kricka L (eds) Bioluminescence and chemiluminescence: current status. John Wiley, Chichester, pp 389–392

  20. Papa ND, Raschi E, Tincani A, Meroni PL (2000) Interaction of antiphospholipid antibodies with endothelial c ells. In: Khamashta MA. Hughes Syndrome: Antiphospholipid Syndrome. Springer, London Berlin Heidelberg, pp 299–304

    Google Scholar 

  21. Persson J, Formgren J, Israelsson B, Berglund G (1994) Ultrasound-determined intima-media thickness and atherosclerosis. Direct and indirect validation. Arterioscler Thromb 14:261–264

    CAS  PubMed  Google Scholar 

  22. Petri M (2000) Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort. Lupus 9:170–175

    Article  CAS  PubMed  Google Scholar 

  23. Petri M, Shoenfeld Y, Matsuura E (2002) Oxidised LDL, not anti-oxidised LDL predicts coronary calcification. Arthritis Rheum 46(Suppl I):S5–54

    Article  Google Scholar 

  24. Reverter JC, Tassies D (2000) Mechanism of thrombosis in the antiphospholipid syndrome: binding to platelets. In: Khamashta MA. Hughes Syndrome: Antiphospholipid Syndrome. Springe, London Berlin Heidelberg, pp 290–298

    Google Scholar 

  25. Salonen JT, Yla-Herttuala S, Yamamoto R (1992) Autoantibody against oxidized LDL and progression of carotid atherosclerosis. Lancet 339:883–887

    Article  CAS  PubMed  Google Scholar 

  26. Steinberg D (1997) Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272:20963–20966

    Article  CAS  PubMed  Google Scholar 

  27. Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    CAS  PubMed  Google Scholar 

  28. Urowitz MB, Gladman DD (2000) Accelerated atheroma in lupus—background. Lupus 9:161–165

    Article  CAS  PubMed  Google Scholar 

  29. Vaarala O (2000) Accelerated atherosclerosis in antiphospholipid syndrome. In: Khamashta MA. Hughes Syndrome: Antiphospholipid Syndrome. Springer, London Berlin Heidelberg, pp 172–178

    Google Scholar 

  30. Vaarala O, Alfthan G, Jauhiainen M et al (1993) Crossreaction between antibodies to oxidised lipoprotein and to cardiolipin in systemic lupus erythematosus. Lancet 341:923–925

    Article  CAS  PubMed  Google Scholar 

  31. Vaarala O (2000) Antibodies to oxidised LDL. Lupus 9:202–205

    Article  CAS  PubMed  Google Scholar 

  32. Van de Vijver LP, Steyger R, van Poppel G, Boer JM, Kruijssen DA, Seidell JC, Princen HM (1996) Autoantibodies against MDA-LDL in subjects with severe and minor atherosclerosis and healthy population controls. Atherosclerosis 122(2):245–253

    Article  CAS  PubMed  Google Scholar 

  33. Wilson WA, Gharavi AE, Koike T et al (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthritis & Rheumatism 7:1309–1311

    Google Scholar 

  34. Witztum JL (1994) The oxidation hypothesis of atherosclerosis. Lancet 344:793–795

    Article  CAS  PubMed  Google Scholar 

  35. Wu R, Nityanand S, Berglund L, Lithell H, Holm G, Lefvert AK (1997) Antibodies against cardiolipin and oxidatively modified LDL in 50-year-old men predict myocardial infarction. Arterioscler Thromb Vasc Biol 17:3159–3163

    CAS  PubMed  Google Scholar 

  36. Wu R, Svenungsson E, Gunnarsson, I, Haegerstrand-Gillis C, Andersson B et al (1999) Antibodies to adult human endothelial cells cross-react with oxidized low-density lipoprotein and beta 2-glycoprotein I (beta 2-GPI) in systemic lupus erythematosus. Clin Exp Immunol 115:561–566

    Article  CAS  PubMed  Google Scholar 

  37. Wuppermann T et al (2000) In: Ultraschallkurs der Gefäße. Urban & Fischer, München Jena 51–53

Download references

Author information

Authors and Affiliations

  1. Med. Klinik III, Bereich Rheumatologie, Universitätsklinikum Carl Gustav Carus, Fetscherstr. 74, 01307, Dresden, Germany

    B. Roch &  H.-E. Schröder

  2. Med. Klinik III, Bereich Pathologische Biochemie, Univ.-Klinikum Carl Gustav Carus, Fetscherstr. 74, 01307, Dresden, Germany

    S. Kopprasch

  3. Forschungszentrum Rossendorf, Institut für Bioanorganische und Radiopharmazeutische Chemie, 510119, 01314, Dresden, Germany

    J. Pietzsch

Authors
  1. B. Roch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Kopprasch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Pietzsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H.-E. Schröder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. Roch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roch, B., Kopprasch, S., Pietzsch, J. et al. Oxidativ modifizierte Lipoproteine und deren Antikörper bei Patienten mit Antiphospholipidsyndrom und Systemischem Lupus erythematodes. Z Rheumatol 63, 331–337 (2004). https://doi.org/10.1007/s00393-004-0601-8

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-004-0601-8

Schlüsselwörter

Key words

Search

Navigation