RSS-Feed abonnieren
DOI: 10.1160/TH07-07-0447
The antigenic binding sites of autoantibodies to factor XII in patients with recurrent pregnancy losses
Publikationsverlauf
Received: 12. Juli 2007
Accepted after major revision: 11. Januar 2007
Publikationsdatum:
24. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200802/lookinside/thumbnails/10-1160-th07-07-0447-1.jpg)
Summary
Recently, numerous studies have suggested an association between factor XII (FXII) deficiency and recurrent pregnancy losses, and between autoantibodies to FXII and recurrent pregnancy losses. Autoantibodies to FXII rather than FXII deficiency may be a risk factor for recurrent pregnancy losses. To know the pathogenesis of autoantibodies to FXII, epitope mapping study was done. Seventeen anti-FXII antibody positive recurrent pregnancy loss patients were chosen for this study. We used synthetic peptides in inhibition and direct binding studies to identify the antigenic binding site of autoantibodies to FXII. Among plasmas from 17 recurrent pregnancy loss patients who were positive for autoantibodies to FXII, 13 patients (76.5%) recognized amino acids 1–30, the amino-terminal heavy chain region that is known as factor XII binding site to platelet glycoprotein Ibα.
Keywords
Recurrent pregnancy losses - factor XII - kininogen - kallikreinkinin system - antiphosphatidylethanolamine antibody - platelet* Both authors contributed equally to this report.
-
References
- 1 Colman RW, Schmaier AH. Contact system: A vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. Blood 1997; 90: 3819-3843.
- 2 Wuepper KD, Miller DR, Lacombe MJ. Flaujeac trait. Deficiency of human plasma kininogen. J Clin Invest 1975; 56: 1663-1672.
- 3 Saito H, Ratnoff OD, Waldmann R. et al. Fitzgerald trait: Deficiency of a hitherto unrecognized agent, Fitzgerald factor, participating in surface mediated reactions of clotting, fibrinolysis, generation of kinins, and the property of diluted plasma enhancing vascular permeability (PF/DIL). J Clin Invest 1975; 55: 1082.
- 4 Halbmayer WM, Haushofer A, Schon A. et al. The prevalence of moderate and severe factor XII (Hageman factor) deficiency among the normal population: Evaluation of the incidence of factor XII deficiency among 300 healthy blood donors. Thromb Haemost 1994; 71: 68-72.
- 5 Lammle B, Wuillemin WA, Huber I. et al. Thromboembolism and bleeding tendency in congenital factor XII deficiency-A study on 74 subjects from 14 swiss families. Thromb Haemost 1991; 65: 117-121.
- 6 Halbmayer WM, Mannhalter C, Feichtinger C. et al. The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism. Thromb Haemost 1992; 68: 285-290.
- 7 Mannhalter C, Fischer M, Hopmeier P. et al. Factor XII activity and antigen concentrations in patients suffering from recurrent thrombosis. Fibrinolysis 1987; 1: 259-263.
- 8 Jespersen J, Munkvad S, Pedersen OD. et al. Evidence for a role of factor XII-dependent fibrinolysis in cardiovascular diseases. Ann NY Acad Sci 1992; 667: 454.
- 9 Oguchi S, Ito D, Murata M. et al. Genotype distribution of the 46C/T polymorphism of coagulation factor XII in the Japanese population: absence of its association with ischemic cerebrovascular disease. Thromb Haemost 2000; 83: 178-179.
- 10 Schved JF, Dupaigne D, Gris JC. et al. Factor XII congenital deficiency and early spontaneous abortion. Fertil Steril 1989; 52: 335-336.
- 11 Braulke I, Hinney B, Pruggmayer M. et al. Factor XII (Hageman) deficiency in women with habitual abortion: new subpopulation of recurrent aborters?. Fertil Steril 1993; 59: 98-101.
- 12 Gris JC, Neveu SR, Maugard C. et al. Prospective evaluation of the prevalence of haemostasis abnormalities in unexplained primary early recurrent miscarriages. Thromb Haemost 1997; 77: 1096-1103.
- 13 McIntyre JA, Wagenknecht DR, Sugi T. Phospholipid binding plasma proteins required for antiphospholipid antibody detection-an overview. Am J Reprod Immunol 1997; 37: 101-110.
- 14 Sugi T, McIntyre JA. Autoantibodies to phosphatidylethanolamine (PE) recognize a kininogen-PE complex. Blood 1995; 86: 3083-3089.
- 15 Sugi T, Katsunuma J, Izumi S. et al. Prevalence and heterogeneity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses. Fertil Steril 1999; 71: 1060-1065.
- 16 Sugi T, Matsubayashi H, Inomo A. et al. Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid-to-late pregnancy loss. J Obstet Gynaecol Res 2004; 30: 326-332.
- 17 Gallimore MJ, Jones DW, Winter M. Factor XII determinations in the presence and absence of phospholipid antibodies. Thromb Haemost 1998; 79: 87-90.
- 18 Jones DW, Gallimore MJ, Harris S. et al. Antibodies to FXII associated with lupus anticoagulant. Thromb Haemost 1999; 81: 387-390.
- 19 Jones DW, Gallimore MJ, Mackie IJ. et al. Reduced factor XII levels in patients with the antiphospholipid syndrome are associated with antibodies to factor XII. Br J Haematol 2000; 110: 721-726.
- 20 Jones DW, Mackie IJ, Gallimore MJ. et al. Antibodies to factor XII and recurrent fetal loss in patients with the anti-phospholipid syndrome. Br J Haematol 2001; 113: 550-552.
- 21 Matsuura T, Kobayashi T, Asahina T. et al. Is factor XII deficiency related to recurrent miscarriage?. Semin Thromb haemost 2001; 27: 115-120.
- 22 Pauer HU, Renne T, Hemmerlein B. et al. Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo. Thromb Haemost 2004; 92: 503-8.
- 23 Iwaki T, Castellino FJ. Plasma levels of bradykinin are suppressed in factor XII-deficient mice. Thromb Haemost 2006; 95: 1003-1010.
- 24 Puri RN, Zhou F, Hu CJ. et al. High molecular weight kininogen inhibits thrombin-induced platelet aggregation and cleavage of aggregin by inhibiting binding of thrombin to platelets. Blood 1991; 77: 500-507.
- 25 Jiang YP, Muller-Esterl W, Schmaier AH. Domain 3 of kininogens contains a cell-binding site and a site that modifies thrombin activation of platelets. J Biol Chem 1992; 267: 3712-3717.
- 26 Bradford HN, Dela Cadena RA, Kunapuli SP. et al. Human kininogens regulate thrombin binding to platelets through the glycoprotein Ib-IX-V complex. Blood 1997; 90: 1508-1515.
- 27 Reddigari SR, Shibayama Y, Brunnee T. et al. Human Hageman factor (factor XII) and high molecular weight kininogen compete for the same binding site on human umbilical vein endothelial cells. J Biol Chem 1993; 268: 11982-11987.
- 28 Bradford HN, Pixley RA, Colman RW. Human factor XII binding to the glycoprotein Ib-IX-V complex inhibits thrombin-induced platelet aggregation. J Biol Chem 2000; 275: 22756-22763.
- 29 Clarke BJ, Cote HCF, Cool DE. et al. Mapping of a putative surface-binding site for human coagulation factor XII. J Biol Chem 1989; 264: 11497-11502.
- 30 Kunapuli SP, Bradford HN, Jameson BA. et al. Thrombin-induced platelet aggregation is inhibited by the heptapeptide Leu271-Ala277 domain 3 in the heavy chain of high molecular weight kininogen. J Biol Chem 1996; 271: 11228-11234.
- 31 Sanmarco M, Alessi MC, Harle JR. et al. Antibodies to phosphatidylethanolamine as the only antiphospholipid antibodies found in patients with unexplained thromboses. Thromb Haemost 2001; 85: 800-805.
- 32 Sugi T, McIntyre JA. Autoantibodies to kininogenphosphatidylethanolamine complexes augment thrombin-induced platelet aggregation. Thromb Res 1996; 84: 97-109.
- 33 Herwald H, Hasan AAK, Godovac-Zimmermann J. et al. Identification of an endothelial cell binding site on kininogen domain 3. J Biol Chem 1995; 270: 14634-14642.
- 34 Katsunuma J, Sugi T, Inomo A. et al. Kininogen domain 3 contains regions recognized by antiphosphatidylethanolamine antibodies. J Thromb Haemost 2003; 1: 132-138.
- 35 Harris SL, Jones DW, Gallimore MJ. et al. The antigenic binding site(s) of antibodies to factor XII associated with the antiphospholipid syndrome. J Thromb Haemost 2005; 3: 969-975.