Autoantibodies to Phospholipids and to the Coagulation Proteins in AIDS

Summary

In HIV-1 infection, an increased prevalence of anticardiolipin autoantibodies (aCL) and lupus anticoagulant (LA) has been described. In order to see if these antibodies are isolated or, like in autoimmune diseases, associated with hematological disorders and with antibodies to other phospholipids and to proteins of coagulation, we investigated 3 groups of patients: 1. 342 HIV-1 infected patients, 2. 145 control patients including 61 systemic lupus erythematosus (SLE) patients, 58 patients with a connective tissue disease, 15 patients with stroke, 11 patients with syphilis and 3.100 blood donors. In HIV-1 infection antiprothrombin (aPrT) antibodies were present in 25% of patients, the prevalence of antiphosphatidylcholine antibodies (aPC) (50%) was almost as high as aCL (64%), and 39% had both antibodies. Absorption on liposomes of the latter revealed an heterogeneous mixture of aCL and aPC or cross-reacting antibodies. In contrast with SLE, anti-β2-glycoprotein I (4%), LA (1%), biological false positive test for syphilis (0.3%), thrombosis (p <0.001) were uncommon. In HIV-1 infection, antiphospholipid antibodies do not associate with features linked to them in SLE or syphilis.

• References

• 1 Wasserman A, Neisser A, Brock C. Eine serodiagnostische Reaktion bei Syphilis. Dtsch Med Wochenschr 1906; 32: 745-746
• 2 Pangborn MC. A new serologically active phospholipid from beef heart. Proc Soc Exp Biol Med 1941; 48: 484-486
• 3 Harris EN, Gharavi AE, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GRV. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2: 1211-1213
• 4 Lockshin MD, Druzin ML, Goei S, Qamar T, Magid MS, Jovanovic L, Ferenc M. Antibodies to cardiolipin as a predictor of fetal distress or death in pregnant patients with SLE. N Engl J Med 1985; 313: 152-156
• 5 Harris EN, Asherson RA, Gharavi AE, Morgan SH, Derue G, Hughes GRV. Thrombocytopenia in SLE and related autoimmune disorders: association with anti cardiolipin antibody. Br J Haematol 1985; 59: 227-230
• 6 Harris EN. Syndrome of the black swan. Br J Rheumatol 1987; 26: 324-326
• 7 Colaco CB, Male DK. Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: distinct profiles of epitope specificity. Clin Exp Imunol 1985; 59: 449-456
• 8 Colaco CB, Mackie IJ, Irving W, Machin SJ. Anticardiolipin antibodies in viral infection. Lancet 1989; 2: 622 (letter).
• 9 Love PE, Santoro SA. Anti-phospholipid antibodies: Anticardiolipin and lupus anticoagulant in systemic lupus erythematosus (SLE) and in non SLE disorders. Ann Int Med 1990; 112: 682-698
• 10 Thirumalai S, Kirshner HS. Anticardiolipin antibody and stroke in an HIV-positive patient. N AIDS 1994; 8: 1019-1020
• 11 Cappell MS, Simon T, Tiku M. Splenic infarction associated with anticardiolipin antibodies in a patient with acquired immunodeficiency syndrome. Dig Dis Sci 1993; 38: 1152-1155
• 12 Mc NeilHP, Simpson RJ, Chersterman CN, Krilis SA. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2Gly coprotein I (apolipoprotein H). Proc Natl Acad Sci USA 1990; 87: 4120-4124
• 13 Matsuura E, Igarashi Y, Fuijimoto M, Ichikawa K, Suzuki T, Sumida T, Yasuda T, Koike T. Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J Immunol 1992; 148: 3885-3891
• 14 Hunt JE, Mc NeilP, Morgan GJ, Crameri RM, Krilis AS. A phospholipid β2 glycoprotein I complex is an antigen for aCL antibodies occurring in autoimmune disease but not with infection. Lupus 1992; 1: 75-81
• 15 Galli M, Comfurius P, Maassen C, Hemker HC, De BaetsMH, Van Brieda-VriesmanPJC, Barbui T, Zwaal RFA, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-1547
• 16 Arvieux J, Roussel B, Jacob MC, Colomb MG. Measurement of anti-phospholipid antibodies by ELISA using β2 glycoprotein I as an antigen. J Imm Meth 1991; 143: 223-229
• 17 Keeling DM, Wilson AJG, Mackie IJ, Machin SJ, Isenberg DA. Some “antiphospholipid antibodies” bind to β2-glycoprotein I in the absence of phospholipid. Br J Haematol 1992; 82: 571-574
• 18 Laperche S, Abuaf N, Meyer O, Carsique R, Deschamps A, Rajoely B, Johanet C, Homberg JC. Association of antimitochondrial antibodies type 5 and anti-beta 2 glycoprotein I antibodies. J Rheum 1994; 21: 1678-1683
• 19 Abuaf N, Rajoely B, Barthet C, Deschamps A, Bouchet MC, Rouquette AM, Vayssairat M. Prevalence of anti-β2 glycoprotein I and anti-prothrombin antibodies in 2174 patients and 107 healthy controls. Nouv Rev Fr Hematol 1995; 37: S53-S56
• 20 Viard JP, Amoura Z, Bach JF. Association of anti-β2 glycoprotein I with lupus type circulating anticoagulant and thrombosis in systemic lupus erythematosus. Am J Med 1992; 93: 181-186
• 21 Bevers EM, Galli M, Barbui T, Comfurius P, Zwaal RFA. Lupus anticoagulant IgG’s (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost 1991; 66: 629-632
• 22 Arvieux J, Damige L, Caron C, Reber G, Bensa JC, Colomb MG. Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants. Thromb Haemost 1995; 74: 1120-1125
• 23 Cunningham AJ. Large numbers of cells in normal mice produce antibody components of isologous erythrocytes. Nature 1974; 252: 749-751
• 24 Mercolino TJ, Arnold LW, Hawkins LA, Haughton G. Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidylcholine. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes. J Exp Med 1988; 168: 687-698
• 25 Cox KO, Hardy SJ. Autoantibodies against mouse bromelain-modified RBC are specifically inhibited by a common membrane phospholipid, phosphatidylcholine. Immunology 1985; 55: 263-268
• 26 Cabral AR, Cabiedes J, Alarcon-Segovia D. Hemolytic anemia related to an IgM autoantibody to phosphatidylcholine that binds in vitro to stored and to bromelain-treated erythrocytes. J Autoimmunity 1990; 3: 773-787
• 27 Staub HL, Harris EN, Khamashta MH, Savidge G, Chahade WH, Hughes GRV. Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis. Ann Rheum Dis 1989; 48: 166-169
• 28 Karmochkine M, Cacoub P, Piette JC, Godeau P, Boffa MC. Antiphosphat-idylethanolamine antibody as the sole antiphospholipid antibody in systemic lupus erythematosus with thrombosis. Clin Exp Rheum 1992; 10: 603-605
• 29 Sugi T, McIntyre JA. Autoantibodies to phosphatidylethanolamine (PE) recognize a kininogen-PE complex. Blood 1995; 86: 3083-3089
• 30 Tan EN, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for classification of systemic lupus erythematosus. Arthr Rheum 1982; 25: 1271-1277
• 31 Centers for Disease Control. Classification system for human T-lymphotropic virus type III/lymphadenopathy-associated virus infection. MMWR 1986; 35: 334-339
• 32 Canoso RT, Zon LI, Groopman JE. Anticardiolipin antibodies associated with HTLV-III infection. Br J Haematol 1987; 65: 495-498
• 33 Mizutani WT, Woods VL, Mc CutchanJA, Zvaifler NJ. Anticardiolipin antibodies in human immunodeficiency virus infected gay males may be associated with a deteriorating clinical course. Arthritis Rheum 1988; 31 (suppl) S 25
• 34 Panzer S, Stain C, Hard H, Dudczak R, Leichner K. Anticardiolipin antibodies are elevated in HIV-1 infected haemophiliacs but do not predict for disease progression. Thromb Haemost 1989; 61: 81-85
• 35 Stimmler MM, Quismorio FP, McGehee WG, Boylen T, Sharma OMP. Anticardiolipin antibodies in acquired immunodeficiency syndrome. Arch Intern Med 1989; 149: 1833-1835
• 36 Capel P, Janssens A, Clumeck N, Gerard M, Feremans W, Vandevelde D, Fondu P. Anticardiolipin antibodies (aCL) are most often not associated with Lupus-Like Anticoagulant (LLA) in Human Immunodeficiency Virus (HIV) infection. Am J Hematol 1991; 37: 234-238
• 37 Intrator L, Oksenhendler E, Desforges L, Bierling P. Anticardiolipin antibodies in HIV infected patients with or without immune thrombocytopenic purpura. Br J Haematol 1988; 62: 269-270
• 38 Bernard C, Exquis B, Reber G, de MoerlooseP. Determination of anticardiolipin and other antibodies in HIV-1 infected patients. J AIDS 1990; 3: 536-539
• 39 Kelsey PR, Stevenson KJ, Poller L. The diagnosis of lupus anticoagulants by the activated partial thromboplastin time. The central role of phosphatidyl serine. Thromb Haemost 1984; 52: 172-175
• 40 Meyer O, Abuaf N, Cyna L, Homberg JC, Kahn MF, Ryckewaert A. Antimitochondrial type 5 antibodies and anti-cardiolipin antibodies in systemic lupus erythematosus and auto-immune diseases. Clin Exp Immunol 1987; 69: 485-492
• 41 Conger JD, Sage HJ, Kawaguchi S, Corley R. Properties of murine antibodies from different V region families specific for bromelain-treated mouse erythrocytes. J Immunol 1991; 146: 1216-1219
• 42 Cohen AJ, Philips TM, Kessler CM. Circulating coagulation inhibitors in the acquired immunodeficiency syndrome. Ann Intern Med 1986; 104: 175-180
• 43 Gold JE, Haubenstock A, Zalusky R. Lupus anticoagulant and AIDS. N Engl J Med 1986; 314: 1252-1253
• 44 Bloom EJ, Abrams DI, Rodgers G. Lupus anticoagulant in the acquired immunodeficiency syndrome. JAMA 1986; 256: 491-493
• 45 Di PrimaMA, Sorice M, Vullo V, Mastroianni CM, Amendolea MA, Masala C. Anticardiolipin antibody in the acquired immunodeficiency syndrome: a marker of pneumocystis carinii infection?. J Infect 1989; 18: 100-101
• 46 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
• 47 Bernard C, de MoerlooseP, Tremblet C, Reger G, Didierjean L. Biological true and false serological tests for syphilis: their relationship with anticardiolipin antibodies. Dermatol 1990; 180: 151-153
• 48 Rauch J, Janoff AS. Phospholipid in the hexagonal II phase is immunogenic: Evidence for immunorecognition of nonbilayer lipid phases in vivo. Proc Natl Acad Sci (USA) 1990; 87: 4112-4114
• 49 Ballem PJ, Belzberg A, Devine DV, Lyster D, Spruston B, Chambers H, Doubroff P, Mikilash K. Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. N Engl J Med 1992; 327: 1779-1784
• 50 Rubbert A, Bock E, Schwab J, Marienhagen J, Nublein H, Wolf F. Anti-cardiolipin antibodies in HIV infection: association with cerebral perfusion defects as detected by ^99mTc-HMPAO SPECT. Clin Exp Immunol 1994; 98: 361-368
• 51 Matsuda J, Saitoh N, Tsukamoto M, Gohchi K, Asami K, Hashimoto M. Measurement of β2-glycoprotein I (apolipoprotein H)-independent anti-cardiolipin antibody in human immunodeficiency virus-1-positive and -negative hemophiliacs. Am J Hematol 1993; 43: 146-148
• 52 Igarashi M, Matsuura E, Igarashi Y, Nagae H, Ichikawa K, Triplett DA, Koike T. Human p2-glycoprotein I as an anticardiolipin cofactor determined using deleted mutants expressed by a baculovirus system. Blood 1996; 87: 3262-3270
• 53 Matsuura E, Igarashi Y, Yasuda T, Triplett DA, Koike T. Anticardiolipin antibodies recognize p2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179: 457-462
• 54 Abuaf N, Laperche S, Deschamps A, Rajoely B, Arvieux J, Girard PM, Rozenbaum W, Rouquette AM. Antiphospholipid sera from systemic lupus erythematosus and AIDS patients are different in their reactivity against β2-glycoprotein I. XIV Congress of the International Society on Thrombosis and Haemostasis, New York. 08/1993. Ed. Schattauer; Stuttgart-New York: 2413 (Abstr.)
• 55 Pengo V, Biasiolo A, Brocco T, Ruffati A. Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies. Thromb Haemost 1996; 75: 721-724
• 56 Loizou S, McCrea J, Rudge AC, Reynolds R, Boyle CC, Harris EN. Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA). Standardization and quantitation of results. Clin Exp Immunol 1985; 62: 738-745
• 57 Forastiero RR, Martinuzzo ME, Kordich LC, Carrera LO. Reactivity to β2 glycoprotein I clearly differentiates anticardiolipin antibodies from antiphospholipid syndrome and syphilis. Thromb Haemost 1996; 75: 717-720
• 58 Alving CR. Antibodies to lipid membranes: Reactions with phosphatidylcholine, cholesterol, liposomes and bromelin-treated erythrocytes. In: Phospholipid-binding antibodies. Harris EN, Exner T, Hughes GRV, Asherson RA. eds. Boca Raton, FL: CRC; 1990: 73