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The prevalence and clinical significance of antiphospholipid antibodies in rheumatoid arthritis

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Abstract

Published data were reviewed to evaluate the occurrence of antiphospholipid antibodies (aPL) in rheumatoid arthritis (RA) patients and to investigate their clinical relevance in this population. The mean prevalence was calculated at 28% and the median was 22%. Few studies have found a relationship between aPL antibodies and thrombosis, particularly in combination with other risk factors. Conflicting results have been reported on the association of anticardiolipin (aCL) antibody positivity and neurologic symptoms, Reynaud’s phenomenon, disease activity, radiographic erosions, extra-articular RA manifestations, rheumatoid factor, and atherosclerosis. Some studies, however, suggest that there is a correlation present between those antibodies and C-reactive protein levels, rheumatoid nodules, and antinuclear antibodies. TNF-α blocking agents may cause an induction of aCL antibodies, but it seems like they do not cause any clinical features related to the antiphospholipid syndrome. Higher 17β-estradiol levels were observed in aCL antibody-positive RA patients than in aCL antibody-negative patients and especially in premenopausal women, which may predispose to a more efficient immune response.

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References and Recommended Reading

  1. Levine JS, Branch DW, Rauch J: The antiphospholipid syndrome. N Engl J Med 2002, 346:752–763. Extensive review of aPL antibodies and APS including the classification criteria and therapy.

    Article  PubMed  CAS  Google Scholar 

  2. Merrill J T: Which antiphospholipid antibody tests are most useful? Rheum Dis Clin North Am 2001, 27:525–549.

    Article  PubMed  CAS  Google Scholar 

  3. de Groot PG, Derksen RHWM: Specificity and clinical relevance of lupus anticoagulant. Vessels 1995, 1:22–26.

    Google Scholar 

  4. Levine JS, Branch DW, Rauch J: The antiphospholipid syndrome. N Engl J Med 2002, 346:752–763.

    Article  PubMed  CAS  Google Scholar 

  5. Galli M: Should we include anti-prothrombin antibodies in the screening for the antiphospholipid syndrome? J Autoimmun 2000, 15:101–105.

    Article  PubMed  CAS  Google Scholar 

  6. de Groot PG, Horbach DA, Simmelink MJ, et al.:Anti-prothrombin antibodies and their relation with thrombosis and lupus anticoagulant. Lupus 1998, 7(Suppl 2):S32-S36.

    Article  PubMed  Google Scholar 

  7. Lopez LR, Dier KJ, Lopez D, et al.: Anti-beta 2-glycoprotein I and antiphosphatidylserine antibodies are predictors of arterial thrombosis in patients with antiphospholipid syndrome. Am J Clin Pathol 2004, 121:142–149.

    Article  PubMed  CAS  Google Scholar 

  8. Lockshin MD: Antiphospholipid antibody syndrome. Rheum Dis Clin North Am 1994, 20:45–59.

    PubMed  CAS  Google Scholar 

  9. Love PE, Santoro SA: Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus er y thematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann Intern Med 1990, 112:682–698.

    PubMed  CAS  Google Scholar 

  10. Roubey RAS: Immunology of the-antiphospholipid syndrome. Arthritis Rheum 1996, 39:1444–1454.

    Article  PubMed  CAS  Google Scholar 

  11. Vaarala O, Palosuo T, Kleemola M: Anticardiolipin responses in acute infections. Clin Immunol Immunopathol 1986, 41:8–15.

    Article  PubMed  CAS  Google Scholar 

  12. Canso RT, De Oliviera RM: Chlorpromazine-induced anticardiolipin antibodies and lupus anticoagulant: absence of thrombosis. Am J Hematol 1988, 27:272–275.

    Article  Google Scholar 

  13. Ordi-Ros J, Selva-O’Callagan A, Monegal-Farran F:Prevalence, significance and specificity of antibodies to phospholipids in Q fever. Clin Infect Dis 1994, 18:213–218.

    PubMed  CAS  Google Scholar 

  14. Petri M: Epidemiology of antiphospholipid antibody syndrome. J Autoimmunity 2000, 15:145–151.

    Article  CAS  Google Scholar 

  15. Schved JF, Dupuy-Fons C, Biron C, et al.: A prospective epidemiological study on the occurrence of antiphospholipid antibody: the Montpellier Antiphospholipid (MAP) Study. Haemostasis 1994, 24:175–182.

    PubMed  CAS  Google Scholar 

  16. Merkel PA, Chang Y, Pierangeli SS, et al.: The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue diseases. Am J Med 1996, 101:576–583.

    Article  PubMed  CAS  Google Scholar 

  17. Cervera R, Khamashta MA, Front J, et al.: Systemic lupus erythematosus: clinical and immunologic paterns of disease expression in a cohort of 1,000 patients. Medicine (Baltimore) 1993, 72:113–124.

    CAS  Google Scholar 

  18. Del Pino-Montes J, López-Bernus A, Pozo L, et al.: Antiphospholipid antibodies in early onset rheumatoid arthritis [abstract]. Paper presented at the Annual European Congress of Rheumatology. Berlin, Germany; June 9–12, 2004.

  19. Vittecoq O, Jouen-Beades F, Krzanowska K, et al.: Prospective evaluation of the frequency and clinical significance of antineutrophil cytoplasmic and anticardiolipin antibodies in community cases of patients with rheumatoid arthritis. Rheumatology (Oxford) 2000, 39:481–489.

    Article  CAS  Google Scholar 

  20. Caporali R, Ravelli A, De Gennaro F, et al.: Prevalence of anticardiolipin antibodies in juvenile chronic arthritis. Ann Rheum Dis 1991, 50:599–601.

    Article  PubMed  CAS  Google Scholar 

  21. Seriolo B, Accardo S, Fasciolo D, et al.: Lipoproteins, anticardiolipin antibodies and thrombotic events in rheumatoid arthritis. Clin Exp Rheumatol 1996, 14:593–599.

    PubMed  CAS  Google Scholar 

  22. Alarcon-Segovia D, Drenkard C: Vasculitis and antiphospholipid syndrome. Rheumatology 2000, 39:922–923.

    Article  PubMed  CAS  Google Scholar 

  23. Seriolo B, Accardo S, Cutolo M: Lipoprotein(a) and other risk factors for thrombosis in rheumatoid arthritis. J Rheumatol 1996, 23:194–196.

    PubMed  CAS  Google Scholar 

  24. Seriolo B, Accardo S, Garnero A, et al.: Anticardiolipin antibodies, free protein S levels and thrombosis: a survey in a selected population of rheumatoid arthritis patients. Rheumatology (Oxford) 1999, 38:675–678.

    Article  CAS  Google Scholar 

  25. Den Heijer M, Rosendaal FR, Blom HJ, et al.: Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Throm Hoemost 1998, 80:874–877.

    Google Scholar 

  26. Gaustadnes M, Ingersler J, Rudiger N: Prevalence of congenital homocystinuria in Denmark [letter]. N Engl J Med 1999, 340:1513.

    Article  PubMed  CAS  Google Scholar 

  27. Ubbink JB, Vermaak WJ, der MerweA, Becker PJ: Vitamin B12, vitamin B6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993, 57:47–53.

    PubMed  CAS  Google Scholar 

  28. Seriolo B, Fasciolo D, Sulli A, Cutolo M: Homocysteine and antiphospholipid antibodies in rheumatoid arthritis patients: relationships with thrombotic events. Clin Exp Rheumatol 2001, 19:561–564.

    PubMed  CAS  Google Scholar 

  29. Fijnheer R, Roest M, Hass FJLM, et al.: Homocysteine, methylenetetrahydrofolate reductase polymorphism, antiphospholipid antibodies, and thromboembolic events in systemic lupus erythematosus: a retrospective cohort study. J Rheumatol 1998, 25:1737–1742.

    PubMed  CAS  Google Scholar 

  30. Wolfe F, Mitchell DM, Sibley JT, et al.: The mortality of rheumatoid arthritis. Arthritis Rheum 1994, 37:481–494.

    Article  PubMed  CAS  Google Scholar 

  31. Buchanan RR, Wardlaw JR, Riglar AG, et al.: Antiphospholipid antibodies in the connective tissue diseases: their relation to the antiphospholipid syndrome and forme fruste disease. J Rheumatol 1989, 16:757–761.

    PubMed  CAS  Google Scholar 

  32. Saraux A, Bendaoud B, Guedes C, et al.: Antiphospholipid antibodies and Raynaud’s phenomenon in rheumatoid arthritis. Clin Exp Rheumatol 1998, 16:351.

    PubMed  CAS  Google Scholar 

  33. Wolf P, Gretler J, Aglas F, et al.: Anticardiolipin antibodies in rheumatoid arthritis: their relation to rheumatoid nodules and cutaneous vascular manifestations. Br J Dermatol 1994, 131:48–51. largest study (173 patients) examining the prevalence of aCL antibodies in R A. The investigators also assessed the clinical relevance and the relationship of those antibodies to skin manifestations

    Article  PubMed  CAS  Google Scholar 

  34. Keane A, Woods R, Dowding V, et al.: Anticardiolipin antibodies in rheumatoid arthritis. Br J Rheumatol 1987, 26:346–350.

    Article  PubMed  CAS  Google Scholar 

  35. Fort JG, Cowchock FS, Abruzzo JL, Smith JB: Anticardiolipin antibodies in patients with rheumatic diseases. Arthritis Rheum 1987, 30:752–760.

    Article  PubMed  CAS  Google Scholar 

  36. Rabee SA, Sallam AM, Ayuoub NM, el Kholy EE: Anticardiolipin antibodies in rheumatoid arthritis. J Egypt Public Health Assoc 1994, 69:47–63.

    PubMed  CAS  Google Scholar 

  37. Wallberg-Jonsson S, Cvetkovic JT, Sundqvist KG, et al.:Activation of the immune system and infiammatory activity in relation to markers of atherothrombotic disease and atherosclerosis in rheumatoid arthritis. J Rheumatol 2002, 29:875–882.

    PubMed  CAS  Google Scholar 

  38. Del Pino-Montes J, López-Bernus A, Belhassen M, et al.: Resence of anticardiolipin antibodies (aCL) in patients with early-onset rheumatoid arthritis (R A) [abstract]. Paper presented at the Annual European Congress of Rheumatolog y. Berlin, Germany; June 9–12, 2004.

  39. Coste J, Jougla E: Mortality from rheumatoid arthritis in France, 1970–1990. Int J Epidemiol 1994, 23:545–552.

    Article  PubMed  CAS  Google Scholar 

  40. Hamsten A, Norberg R, Bjorkholm M, et al.: Antibodies to cardiolipin in young survivors of myocardial infarction: an association with recurrent cardiovascular events. Lancet 1986, 1:113–116.

    Article  PubMed  CAS  Google Scholar 

  41. Morton KE, Gavaghan TP, Krilis SA, et al.: Coronary artery bypass graft failure-an autoimmune phenomenon? Lancet 1986, 2:1353–1357.

    Article  PubMed  CAS  Google Scholar 

  42. Sherer Y, Gerli R, Vaudo G, et al.: Thickened carotid artery intima-media in rheumatoid arthritis is associated with anti-cardiolipin antibodies [abstract]. Paper presented at the Annual European Congress of Rheumatology. Berlin, Germany; June 9–12, 2004.

  43. Weinblatt ME, Kremer JM, Bankhurst AD, et al.: A trial of etanercept a recombinant tumor necrosis factor receptor: Fc fusion protein in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999, 340:253–259.

    Article  PubMed  CAS  Google Scholar 

  44. Moreland LW, Baumgartner SW, Schiff MH, et al.:Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997, 337:141–147.

    Article  PubMed  CAS  Google Scholar 

  45. Ferraccioli G, Mecchia F, Di Poi E, Fabris M: Anticardiolipin antibodies in rheumatoid patients treated with etanercept or conventional combination therapy: direct and indirect evidence for a possible association with infections. Ann Rheum Dis 2002, 61:358–361.

    Article  PubMed  CAS  Google Scholar 

  46. Jonsdottir T, Forslid J, van Vollenhoven A, et al.: Treatment with tumour necrosis factor alpha antagonists in patients with rheumatoid arthritis induces anticardiolipin antibodies. Ann Rheum Dis 2004, 63:1075–1078. s is the largest published study (121 patients) evaluating the frequency and clinical impact of aCL antibodies in patients with RA treated with TNF-á inhibitors.

    Article  PubMed  CAS  Google Scholar 

  47. Gómez-Puerta JA, Hernández MV, Reverter JC, et al.: Anticardiolipin antibodies in patients with rheumatoid arthritis and spondyloarthopathies treated with inf liximab [abstract]. Paper presented at the Annual European Congress of Rheumatolog y. Berlin, Germany; June 9–12, 2004.

  48. Bobbio-Pallavicini F, Alpini C, Caporali R, et al.:Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment. Arthritis Res Ther 2004, 6:R264-R272.

    Article  PubMed  CAS  Google Scholar 

  49. Ferraro-Peyret C, Coury F, Tebib JG, et al.: Infliximab therapy in rheumatoid arthritis and ankylosing spondylitis- induced specific antinuclear and antiphospholipid autoantibodies without autoimmune clinical manifestations: a two-year prospective study. Arthritis Res Ther 2004, 6:R535-R543.

    Article  PubMed  CAS  Google Scholar 

  50. Jonsdottir T, Forslid J, van Vollenhoven A, et al.: Treatment with tumour necrosis factor alpha antagonists in patients with rheumatoid arthritis induces anticardiolipin antibodies. Ann Rheum Dis 2004, 63:1075–1078.

    Article  PubMed  CAS  Google Scholar 

  51. Isomãki P, Punnonen J: Pro- and anti-inflammatory cytokines in rheumatoid arthritis. Ann Med 1997, 29:499–507.

    PubMed  Google Scholar 

  52. Cutolo M, Sulli A, Seriolo B, Masi MT: Estrogens, the immune response and autoimmunity. Clin Exp Rheumatol 1995, 13:217–226.

    PubMed  CAS  Google Scholar 

  53. Seriolo B, Cutolo M, Garnero A, Accardo S: Relationships between serum 17 beta-oestradiol and anticardiolipin antibody concentrations in female patients with rheumatoid arthritis. Rheumatology (Oxford) 1999, 38:1159–1161.

    Article  CAS  Google Scholar 

  54. Seriolo B, Accardo S, Garnero A, et al.: Association between anticardiolipin antibody positivity and increased 17-beta-estradiol levels in premenopausal women with rheumatoid arthritis. Ann N Y Acad Sci 1999, 876:159–163.

    Article  PubMed  CAS  Google Scholar 

  55. Kaburaki J, Kuwana M, Yamamoto M, et al.: Disease distribution of beta 2-glycoprotein 1-dependent anticardiolipin antibodies in rheumatic diseases. Lupus 1995, 4:27S-31S.

    Google Scholar 

  56. Jurado M, Paramo JA, Gutierrez-Pimentel M, Rocha E:Fibrinolytic potential and antiphospholipid antibodies in systemic lupus er ythematosus and other connective tissue disorders. Thromb Haemost 1992, 68:516–520.

    PubMed  CAS  Google Scholar 

  57. Merkel PA, Chang Y, Pierangeli SS, et al.: The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue diseases. Am J Med 1996, 101:576–583.

    Article  PubMed  CAS  Google Scholar 

  58. Ambrozic A, Bozic B, Hojnik M, et al.: Antiphospholipid antibodies and rheumatoid arthritis. Ann Rheum Dis 2002, 61:85–86.

    Article  PubMed  CAS  Google Scholar 

  59. Marai I, Gilburd B, Blank M, Shoenfeld Y: Anti-cardiolipin and anti-beta2-glycoprotein I (beta2GP-I) antibody assays as screening for anti-phospholipid syndrome. Hum Antibodies 2003, 12:57–62.

    PubMed  CAS  Google Scholar 

  60. Sherer Y, Gerli R, Vaudo G, et al.: Prevalence of antiphospholipid and antioxidized low-density lipoprotein antibodies in rheumatoid arthritis. Ann N Y Acad Sci 2005, 1051:299–303.

    Article  PubMed  CAS  Google Scholar 

  61. Assous N, Allanore Y, Batteux F, et al.: Prevalence of antiphospholipid antibodies in systemic sclerosis and association with primitive pulmonary arterial hypertension and endothelial injury. Clin Exp Rheumatol 2005, 23:199–204.

    PubMed  CAS  Google Scholar 

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  1. Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, 825 Northeast 13th St, 73104, Oklahoma City, OK, USA

    Ewa Olech MD

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  1. Ewa Olech MD
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  2. Joan T. Merrill MD
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Correspondence to Ewa Olech MD.

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Olech, E., Merrill, J.T. The prevalence and clinical significance of antiphospholipid antibodies in rheumatoid arthritis. Curr Rheumatol Rep 8, 100–108 (2006). https://doi.org/10.1007/s11926-006-0049-8

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