Conclusions
Our observations, and those from others, give further support to our hypothesis that “autoimmune aPL” may be generated by immunization with products from bacteria or viruses after incidental exposure or infection. We also were able to generate APS-like syndrome in a strain of mice susceptible to autoimmunity, indicating that other factors are likely to be involved, such as genetic predisposition. Furthermore, not all aPL generated were pathogenic. Based on the clinical experience and on the numerous reports indicating presence of aPL in large number of infectious diseases, it may be expected that not all aPL produced during infection will be pathogenic. A limited number aPL induced by certain viral/bacterial products would be pathogenic in certain genetically predisposed individuals. Further studies to identify the agents responsible for induction the pathogenic aPL are needed. Identification of those bacterial and/or viral agents may help finding strategies for the prevention of production of aPL “pathogenic” antibodies. Alternatively, free peptides may be used to induce tolerance against aPL production or to abrogate their pathogenic effects.
Drugs such as procainamide and phenothiazines can also induce aPL. The prevalence and pathogenicity of drug-induced aPL is generally low and has been discussed in this chapter.
Keywords
- Anticardiolipin Antibody
- Systemic Lupus Erythemato
- Hughes Syndrome
- Lupus Anticoagulant Activity
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
In memory of A.E. Gharavi who passed away on Oct 13, 2004.
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References
Wasserman A, Neisser A, Bruck C. Eine serodiagnostiche Reaction bei Syphilis. Dtsch Med Wochenschr 1906;32:745–489.
Gharavi AE, Wilson WA. Antiphospholipid antibodies, In: Wallace DJ, Hahn, eds. Lupus erythematosus, 5th ed. Philadelphia: Williams & Wilkins; 1996:471–491.
Lockshin MD, Druzin ML, Goei S, et al. Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus. N Engl J Med 1985;313:152–156.
Lansdteiner K, Muller R, Potzl O. Zur Frage der Komplementbindungsreaktion bei Syphilis. Wein Klin Wochenschr 1907;20:1565–1569.
Pangborn MC. A new serologically active phospholipid from beef heart. Proc Soc Exp Biol Med 1941;48:484–486.
Harris A, Rosenberg AA, Riedel L. A microflocculation test for syphilis using cardiolipin antigen. Preliminary report. J Vener Dis Inf 1946;27:169–174.
Moore JE, Mohr CF. Biologically false-positive test for syphilis: type, incidence, and cause. J Am Med Assoc 1952;150:467–473.
Putkonen T, Jokinen EJ, Foerstroem L. Reiter protein complement fixation test in treated neurosyphilis. Acta Derm Venereol 1963;43:405–412.
Lynch FW, Boynton RE, Kimball AC. False positive serologic reactions for syphilis due to smallpax vaccination (vaccinia) J Am Med Assoc 1941;115:591–595.
Moore JE, Lutz WB. Natural history of SLE: approach to its study through chronic biologic false positive reactions. J Chron Dis 1949;1:297–316.
Harvey AM, Shulman LE. Systemic lupus erythematosus and chronic biological false-positive test for syphilis. In: Dubouis E, ed. Lupus, 4th ed. Los Angeles: University of California Press; 1974:196–209.
Laurell AB, Nilsson IM. Hypergammaglobulinemia and biological false positive Wassermann reaction: a study of two cases. J Lab Clin Med 1957;49:694–707.
Lee SL, Saunders M. A disorder of blood coagulation in SLE. J Clin Invest 1955;34:1814–1822.
Thiagarajan P, Shapiro SS, DeMarco L. Monoclonal immunoglobulin M lambda coagulation inhibitor with phospholipid specificity: mechanism of lupus anticoagulant. J Clin Invest 1980;66:397–407.
Bowie EJ, Thompson JH Jr, Pascuzzi CA, et al. Thrombosis in SLE despite cirulating anticoagulants. J Lab Clin Med 1963;62:416–420.
Harris EN, Gharavi AE, Boey M, et al. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983;ii:1211–1214.
Gharavi AE, Harris EN, Asherson RA, Hughes GRV. Antiphospholipid antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis 1987;46:1–6.
Harris EN, Gharavi AE, Patel BM, Hughes GRV. Evaluation of the anticardiolipin antibody test: report of an international workshop held April 4 1986. Clin Exp Immunol 1987;68:215–222.
Harris EN, Gharavi AE, Loizou S, et al. Cross-reactivity of antiphospholipid antibodies. J Clin Lab Immunol 1985;16:1–6.
Wilson WA, Gharavi AE. Hughes syndrome: perspectives on thrombosis and antiphospholipid antibody. Am J Med 1996;101:574–576.
Vaarala O, Kleemola M, Palosuo T, Aho K. Anticardiolipin in response in acute infections. Clin Immunol Immunopathol 1986;41:8–15.
Mackworth-Young CG, Harris EN, Steere AC, et al. Anticardiolipin antibodies in Lyme disease. Arthritis Rheum 1988;31:1052–1057.
Catteau B, Delaporte E, Hachulla E, et al. Mycoplasma infection with Stevens-Johnson syndrome and antiphospholipid antibodies: apropos of 2 cases. Rev Med Interne 1995;16:10–14.
Santiago MB, Cossemelli W, Tuma MF, Oliveira RM. Anticardiolipin antibodies in infectious diseases. Clin Rheumatol 1989;8:23–28.
Fiallo P, Ninzi. β2glycoprotein I-dependent anticardiolipin antibodies as a risk factor for reactions in borderline leprosy patients. Int J Lepr Other Mycobact Dis 1998;66:387–388.
Durupt S, Rosselli S, Manchon J, Lopez M. Presence of antiphospholipid antibodies in “Legionnaires disease”. Presse Med 1996;25:1649.
Galvez J, Martin I, Medino D, Pujol E. Thrombophlebitis in a patient with abute Q fever and anticardiolipin antibodies. Med Clin (Barc) 1997;108:396–397.
Chaumentin G, Zenone T, Bibollet C, et al. Malignant boutonneuse fever and polymyalgia rheumatica: a coincidental association? Infection 1997;25:320–322.
Labarca JA, Rabaggliatti RM, Radrigan FJ, et al. Antiphospholipid syndrome associated with cytomegalovirus infection: case report and review. Clin Infect Dis 1997;24:197–200.
Manco-Johnson MJ, Nuss R, Key N, Moertel C, et al. Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis. J Pediatr 1996;128:319–323.
Intrator L, Oksenhendler E, Desforgs L. Anticardiolipin antibodies in HIV infected patients with or without autoimmune thrombocytopenia purpura. Br J Haematol 1988;67:269–270.
Herzenberg Am, Telford JJ, De Luca LG, et al. Thrombotic microangiopathy associated with cryoglobulinemic membranoproliferative glomerulonephritis and hepatitis C. Am J Kidney Dis 1998;31:521–526.
Poux JM, Jauberteau MO, Boudet R, et al. Transient lupus anticoagulant induced by Epstein-Barr virus infections. Blood Coagul Fibrinolysis 1991;2:771–774.
Sammaritano LR, Gharavi AE, Lockshin MD. Antiphospholipid antibody: immunologic and clinical aspects. Semin Arthritis Rheum 1990;20:81–96.
Harris EN, Gharavi AE, Wasley GD, Hughes GRV. Use of an enzyme-linked immunosorbent assay and of inhibition studies to distinguish between antibodies to cardiolipin from patients with syphilis or autoimmune disorders. J Infect Dis 1988;157:23–31.
Harris EN, Pierangeli SS. A more specific ELISA assay for the detection of antiphospholipid antibodies. Clin Immunol 1995;15:26–28.
Levy RA, Gharavi AE, Sammaritano LR, et al. Characteristics of IgG antiphospholipid antibodies in patients with systemic lupus erythematosus and syphilis. J Immunol 1990;17:1036–1041.
Costello PB, Green FA. Reactivity patterns of human anticardiolipin and other antiphospholipid antibodies in syphilitic sera. Infect Immun 1986;51:771–775.
Matsuura H, Igarashi T, Fujimoto M, et al. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease [letter]. Lancet 1990;336:177–178.
Galli M, Comfurius P, Hemker HC, et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990;335:1544–1547.
McNeil HP, Simpson RJ, Chesterman CJ, Krilis SA. Antiphospholipid antibodies are directed against a complex antigen that includes lipid binding inhibitor of coagulation: β2 glycoprotein I (apolipoprotein H). Proc Natl Acad Sci U S A 1990;87:4120–4124.
Gharavi AE, Sammaritano LR, Wen J, et al. Characteristics of HIV and chlorpromazine induced antiphospholipid antibodies: effect of β2glycoprotein I on binding to phospholipid. J Rheumatol 1994;21:94–99.
Hunt J, Krilis S. A phospholipid-β2glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. Lupus 1992;1:75–81.
Celli M, Gharavi AE, Chaimovich H. Opposite β2glycoprotein I requirement for the binding of infectious and autoimmune antiphospholipid antibodies to cardiolipin liposomes is associated with antibody avidity. Biochim Biophys Acta 1999;12:225–238.
Campbell AL, Pierangeli SS, Wellhausen S, Harris EN. Comparison of the effects of anticardiolipin antibodies from patients with the antiphospholipid syndrome and with syphilis on platelet aggregation. Thromb Haemost 1995;73:529–534.
Pierangeli SS, Goldsmith GH, Krnic S, Harris EN. Differences in functional activity of anticardiolipin antibodies from patients with syphilis and the antiphospholipid syndrome. Infect Immun 1994;62:4081–4084.
Matsuura E, Igarashi M, Yasuda T, Koike T, Triplett DA. Anticardiolipin antibodies recognize β2glycoprotein I structure altered by interacting with in oxygen modified solid phase surface. J Exp Med 1994;179:457–462.
Roubey RAS. Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulantas and other “antiphospholipid” autoantibodies. Blood 1994;84:2854–2867.
Tsutsumi A, Matsuura E, Ichikawa K, et al. Antibodies to β2glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus. Arthritis Rheum 1996;39:1466–1474.
Roubey RA. Comparison of an enzyme-linked immunosorbent assay for antibodies to β2glycoprotein I and a conventional anticardiolipin immunoassay. Arthritis Rheum 1996;39:1606–1607.
Forastiero RR, Martinuzzo ME, Kordich LC, Carreras LO. Reactivity to β2glycoprotein I clearly differentiates anticardiolipin antibodies from antiphospholipid syndrome and syphilis. Thromb Haemost 1996;75:717–720.
Leroy V, Arvieux J, Jacob MC, et al. Prevalence and significance of anticardiolipin, anti-β2glycoprotein I and anti-prothrombin antibodies in chronic hepatitis C. Br J Haematol 1998;101:468–474.
Constans J, Guerin V, Couchouron A, et al. Autoantibodies directed against phospholipids or human β2glycoprotein I in HIV-seropositive patients: relationship with endothelial activation and antimalonic dialdehyde antibodies. Eur J Clin Invest 1988;28:115–122.
Hojnik M, Gilburd B, Ziporen L, et al. Anticardiolipin antibodies in infections are heterogenous in their dependency on β2glycoprotein I: analysis of anticardiolipin antibodies in leprosy. Lupus 1994;3:515–521.
Faghri Z, Wilson WA, Taheri F, Barton EN, Morgan OS, Gharavi AE. Antibodies to cardiolipin and β2glycoprotein I in HTLV-1 associated myelopathy tropical spastic para paresis. Lupus 1999;8:210–214.
Loizou S, Cazabon JK, Walport MJ, et al. Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus. Arthritis Rheum 1997;40:103–108.
Giordano P, Galli M, Del Vecchio GC, et al. Lupus anticoagulant, anticardiolipin antibodies and hepatitis C virus infection in thalassemia. Br J Haematol 1998;102:903–906.
Prieto J, Yuste JR, Beloqui O, et al. Anticardiolipin antibodies in chronic hepatitis C: implication of hepatitis C virus as the cause of antiphospholipid syndrome. Hepatology 1997;23:199–204.
Jaeger U, Kapiotis S, Pabinger I, et al. Transient lupus anticoagulant associated with hypoprothrombinemia and factor XII deficiency following adenovirus infection. Ann Hematol 1993;67:95–99.
Uthman I, Tabbarah Z, Gharavi AE. Hughes syndrome associated with cytomegalovirus infection. Lupus 1999;8:775–777.
Gharavi AE, Sammaritano LR, Wen J, Elkon KB. Induction of antiphospholipid autoantibodies by immunization with β2 glycoprotein I (apolipoprotein H). J Clin Invest 1992;90:1105–1109.
Pierangeli SS, Liu XW, Anderson G, et al. Thrombogenic properties of murine anti-cardiolipin antibodies induced by β2 glycoprotein 1 and human IgG antiphospholipid antibodies. Circulation 1996;94:1746–1751.
Pierangeli SS, Harris EN. Induction of phospholipid-binding antibodies in mice and rabbits by immunization with human β2 glycoprotein I or anticardiolipin antibodies alone. Clin Exp Immunol 1993;78:233–238.
Blank M, Fadin D, Tincani A, et al. Immunization with anticardiolipin cofactor (β2-glycoprotein I) induces experimental antiphospholipid antibody syndrome in naive mice. J Autoimmun 1994;7:441–455.
Garcia CO, Kanbour-Shakir A, Tang H, Molina JF, Espinoza LR, Gharavi AE. Induction of experimental antiphospholipid syndrome in PL/J mice following immunization with β2 GPI. Am J Reprod Immunol 1997;37:118–124.
Aron AL, Cuellar ML, Brey RL, et al. Early onset of autoimmunity in MRL/++ mice following immunization with β2-glycoprotein I. Clin Exp Immunol 1995;101:78–81.
Hunt J, Krilis S. The fifth domain of β2 glycoprotein I contains a phospholipid binding site (Cys 281-Lys288) and a region recognized by anticardiolipin antibodies. J Immunol 1994;152:653–659.
Gharavi AE, Tang H, Gharavi E, et al. Induction of aPL by immunization with a 15 amino acid peptide. Arthritis Rheum 1995;39:S296.
Gharavi AE, Pierangeli SS, Colden-Stanfield M, et al. GDKV-induced antiphospholipid antibodies enhance thrombosis and activate endothelial cells in vivo and in vitro. J Immunol 1999;163:2922–2927.
Gharavi EE, Cucurull E, Tang H, et al. Induction of antiphospholipid antibodies by immunization with viral peptides. Lupus 1999;8:449–455.
Gharavi AE, Pierangeli SS, Espinola RG, et al. Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo. Arthritis Rheum 2002;46:545–552.
Gharavi AE, Vega-Ostertag M, Espinola RG, et al. Intrauterine fetal death in mice caused by cytomegalovirus-derived peptide induced aPL. Lupus 2004;13:17–23.
Blank M, Krause I, Fridkin M, et al. Bacterial induction of autoantibodies to β2glycoprotein I accounts for the infection etiology of antiphospholipid syndrome. J Clin Invest 2002;106:797–804.
Pierangeli SS, Blank M, Liu X, et al. A peptide that shares similarity with bacterial antigens reverses thrombogenic properties of antiphospholipid antibodies in vivo. J Autoimmun 2004;22:217–225.
Canoso RT, de Oliveira RM. Chlorpromazine-induced anticardiolipin antibodies and lupus anticoagulant: absence of thrombosis. Am J Hematol 1988;27:272–275.
Triplett DA, Brandt JT, Musgrave KA, Orr CA. The relationship between lupus anticoagulants and antibodies to phospholipids. JAMA 1988;259:550–554.
Derksen RHWM, Kator I. Lupus anticoagulant: revival of an old phenomenon. Clin Exp Rheumatol 1985;3:349–357.
Spiers C, Fielder AHL, Chapel H, Davey NJ, Batchelor JR. Complement system protein C4 and susceptibility to hydralazine-induced systemic lupus erythematosus. Lancet 1989;i:922–924.
Sim E, Gill EW, Sim RB. Drugs that induce systemic lupus erythematosus inhibit complement component C4. Lancet 1984;ii:422–424.
Russell AS, Ziff M. Natural antibodies to procainamide. Clin Exp Immunol 1968;3:901–909.
Blomgren SE, Condemi JJ, Bignall MC. Antinuclear antibody induced by procainamide. A prospective study. N Engl J Med 1969;281:61–66.
Day JH, Cherrey R, O’Hara D, Carabello J. Incidence of procainamide-induced lupus anticoagulants [abstract]. Thromb Haemost 1987;58:394.
Asherson RA, Zulman J, Hughes GRV. Pulmonary thromboembolism associated with procainamide induced lupus syndrome and anticardiolipin antibodies. Ann Rheum Dis 1989;48:232–235.
Schlesinger P, Peterson L. Procainamide-associated lupus anticoagulants and thrombotic events [abstract]. Arthritis Rheum 1988;31:S54.
Li GC, Greenberg CS, Curie MS. Procainamide induced lupus anticoagulants and thrombosis. South Med J 1988;81:262–264.
Zarrabi MH, Zucker S, Miller F, et al. Immunologic coagulation disorders in chlorpromazine-treated patients. Ann Intern Med 1988;81:262–264.
Gharavi AE, Harris EN, Asherson RA, et al. Anticardiolipin (aCL) isotypes: a study of their clinical releance [abstract]. Clin Rheumatol 1986;5:154.
Berglund S, Gottfries CG, Stormby K. Chlorpromazine-induced antinuclear factors. Acta Med Scand 1970;187:67–74.
Mueh JR, Herbst KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980;92:156–159.
Rosa-Re D, Garcia F, Gascon J, et al. Quinine induced lupus-like syndrome and cardiolipin antibodies. Ann Rheum Dis 1996;55:559–560.
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Pierangeli, S.S., Gharavi, A.E. (2006). Infection and Drug-Induced Antiphospholipid Antibodies. In: Khamashta, M.A. (eds) Hughes Syndrome. Springer, London. https://doi.org/10.1007/1-84628-009-5_42
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