Skip to main content
SpringerLink
Log in
Book cover

Hughes Syndrome pp 470–491Cite as

Lessons from Sequence Analysis of Monoclonal Antiphospholipid Antibodies

  • Chapter

Conclusion

From the published sequences of monoclonal aPL there is no evidence that particular human Ig V region genes are used preferentially to encode aPL. Somatic mutations which are antigen driven confer high specificity binding in IgG aPL but do not play a role in the formation of similar binding characteristics in the more specific IgM aPL. We have identified a common factor between these 2 groups of aPL, which is the presence of Arg, Asn, and Lys residues in CDRs and contact sites. These are germline encoded in the more specific IgM aPL but often arise due to somatic mutations in the IgG aPL. Our hypothesis is that the Arg, Asn, and Lys residues increase the affinity of binding via electrostatic interactions and hydrogen bonds with negatively charged epitopes upon PL and domain I of β2-GPI. We have demonstrated the relative importance of certain surface exposed Arg residues at critical positions within the light chain CDR1 and heavy chain CDR3 of different human monoclonal aPL in conferring the ability to bind CL. It is now important to test the effects of sequence changes involving these amino acids on pathogenic functions of these aPL. Such tests may help to define the nature of interactions between aPL, PL, and β2-GPI. This may eventually help in the development of drugs to interfere with those interactions, and thereby improve the treatment of APS.

Keywords

  • Systemic Lupus Erythematosus
  • Light Chain
  • Somatic Mutation
  • Somatic Hypermutation
  • Hughes Syndrome

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.

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999;42:1309–1311.

    CrossRef  PubMed  CAS  Google Scholar 

  2. Loizou S, Mackworth-Young CG, Cofiner C, et al. Heterogeneity of binding reactivity to different phospholipids of antibodies from patients with systemic lupus erythematosus (SLE) and with syphilis. Clin Exp Immunol 1990;80:171–176.

    CrossRef  PubMed  CAS  Google Scholar 

  3. Alarcon-Segovia D, Deleze M, Oria CV, et al. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore) 1989;68:353–365.

    PubMed  CAS  Google Scholar 

  4. Lynch A, Marlar R, Murphy J, et al. Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study. Ann Intern Med 1994;120:470–475.

    PubMed  CAS  Google Scholar 

  5. Galli M, Comfurius P, Maassen C, et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990;335:1544–1547.

    CrossRef  PubMed  CAS  Google Scholar 

  6. McNeil HP, Simpson RJ, Chesterman CN, et al. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci U S A 1990;87:4120–4124.

    CrossRef  PubMed  CAS  Google Scholar 

  7. Matsuura E, Igarashi Y, Fujimoto M, et al. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet 1990;336:177–178.

    CrossRef  PubMed  CAS  Google Scholar 

  8. Ordi J, Selva A, Monegal F, et al. Anticardiolipin antibodies and dependence of a serum cofactor. A mechanism of thrombosis. J Rheumatol 1993;20:1321–1324.

    PubMed  CAS  Google Scholar 

  9. Oosting JD, Derksen RH, Bobbink IW, et al. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism? Blood 1993;81:2618–2625.

    PubMed  CAS  Google Scholar 

  10. Bevers EM, Galli M, Barbui T, et al. 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.

    PubMed  CAS  Google Scholar 

  11. Tsutsumi A, Matsuura E, Ichikawa K, et al. Antibodies to beta 2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus. Arthritis Rheum 1996;39:1466–1474.

    PubMed  CAS  Google Scholar 

  12. McNally T, Mackie IJ, Machin SJ, et al. Increased levels of beta 2 glycoprotein-I antigen and beta 2 glycoprotein-I binding antibodies are associated with a history of thromboembolic complications in patients with SLE and primary antiphospholipid syndrome. Br J Rheumatol 1995;34:1031–1036.

    PubMed  CAS  Google Scholar 

  13. Kandiah DA, Sali A, Sheng Y, et al. Current insights into the “antiphospholipid” syndrome: clinical, immunological, and molecular aspects. Adv Immunol 1998;70:507–563.

    CrossRef  PubMed  CAS  Google Scholar 

  14. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975;256:495–497.

    CrossRef  PubMed  CAS  Google Scholar 

  15. Olsson L, Kaplan HS. Human-human hybridomas producing monoclonal antibodies of predefined antigenic specificity. Proc Natl Acad Sci U S A 1980;77:5429–5431.

    CrossRef  PubMed  CAS  Google Scholar 

  16. Teng NN, Lam KS, Calvo Riera F, et al. Construction and testing of mouse-human heteromyelomas for human monoclonal antibody production. Proc Natl Acad Sci U S A 1983;80:7308–7312.

    CrossRef  PubMed  CAS  Google Scholar 

  17. Chothia C, Lesk AM, Tramontano A, et al. Conformations of immunoglobulin hypervariable regions. Nature 1989;342:877–883.

    CrossRef  PubMed  CAS  Google Scholar 

  18. Wu TT, Kabat EA. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med 1970;132:211–250.

    CrossRef  PubMed  CAS  Google Scholar 

  19. Tonegawa S. Somatic generation of antibody diversity. Nature 1983;302:575–581.

    CrossRef  PubMed  CAS  Google Scholar 

  20. Matsuda F, Shin EK, Nagaoka H, et al. Structure and physical map of 64 variable segments in the 3’0.8-megabase region of the human immunoglobulin heavy-chain locus. Nat Genet 1993;3:88–94.

    CrossRef  PubMed  CAS  Google Scholar 

  21. Cook GP, Tomlinson IM, Walter G, et al. A map of the human immunoglobulin VH locus completed by analysis of the telomeric region of chromosome 14q. Nat Genet 1994;7:162–168.

    CrossRef  PubMed  CAS  Google Scholar 

  22. Schable KF, Zachau HG. The variable genes of the human immunoglobulin kappa locus. Biol Chem Hoppe Seyler 1993;374:1001–1022.

    PubMed  CAS  Google Scholar 

  23. Williams SC, Frippiat JP, Tomlinson IM, et al. Sequence and evolution of the human germline V lambda repertoire. J Mol Biol 1996;264:220–232.

    CrossRef  PubMed  CAS  Google Scholar 

  24. Ignatovich O, Tomlinson IM, Jones PT, et al. The creation of diversity in the human immunoglobulin V(lambda) repertoire. J Mol Biol 1997;268:69–77.

    CrossRef  PubMed  CAS  Google Scholar 

  25. Ignatovich O, Tomlinson IM, Popov AV, et al. Dominance of intrinsic genetic factors in shaping the human immunoglobulin Vlambda repertoire. J Mol Biol 1999;294:457–465.

    CrossRef  PubMed  CAS  Google Scholar 

  26. Brezinschek HP, Foster SJ, Brezinschek RI, et al. Analysis of the human VH gene repertoire. Differential effects of selection and somatic hypermutation on human peripheral CD5(+)/IgM+ and CD5(-)/IgM+ B cells. J Clin Invest 1997;99:2488–2501.

    PubMed  CAS  Google Scholar 

  27. Brezinschek HP, Foster SJ, Dorner T, et al. Pairing of variable heavy and variable kappa chains in individual naive and memory B cells. J Immunol 1998;160:4762–4767.

    PubMed  CAS  Google Scholar 

  28. de Wildt RM, Hoet RM, van Venrooij WJ, et al. Analysis of heavy and light chain pairings indicates that receptor editing shapes the human antibody repertoire. J Mol Biol 1999;285:895–901.

    CrossRef  PubMed  Google Scholar 

  29. de Wildt RM, Tomlinson IM, van Venrooij WJ, et al. Comparable heavy and light chain pairings in normal and systemic lupus erythematosus IgG(+) B cells. Eur J Immunol 2000;30:254–261.

    CrossRef  PubMed  Google Scholar 

  30. Storb U. The molecular basis of somatic hypermutation of immunoglobulin genes. Curr Opin Immunol 1996;8:206–214.

    CrossRef  PubMed  CAS  Google Scholar 

  31. Berek C, Milstein C. The dynamic nature of the antibody repertoire. Immunol Rev 1988;105:5–26.

    CrossRef  PubMed  CAS  Google Scholar 

  32. Wagner SD, Neuberger MS. Somatic hypermutation of immunoglobulin genes. Annu Rev Immunol 1996;14:441–457.

    CrossRef  PubMed  CAS  Google Scholar 

  33. Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB, et al. The role of clonal selection and somatic mutation in autoimmunity. Nature 1987;328:805–811.

    CrossRef  PubMed  CAS  Google Scholar 

  34. Lossos IS, Tibshirani R, Narasimhan B, et al. The inference of antigen selection on Ig genes. J Immunol 2000;165:5122–5126.

    PubMed  CAS  Google Scholar 

  35. Radic MZ, Weigert M. Genetic and structural evidence for antigen selection of anti-DNA antibodies. Annu Rev Immunol 1994;12:487–520.

    CrossRef  PubMed  CAS  Google Scholar 

  36. Rahman A, Latchman DS, Isenberg DA. Immunoglobulin variable region sequences of human monoclonal anti-DNA antibodies. Semin Arthritis Rheum 1998;28:141–154.

    CrossRef  PubMed  CAS  Google Scholar 

  37. MacCallum RM, Martin AC, Thornton JM. Antibody-antigen interactions: contact analysis and binding site topography. J Mol Biol 1996;262:732–745.

    CrossRef  PubMed  CAS  Google Scholar 

  38. Chothia C, Gelfand I, Kister A. Structural determinants in the sequences of immunoglobulin variable domain. J Mol Biol 1998;278:457–479.

    CrossRef  PubMed  CAS  Google Scholar 

  39. Radway-Bright EL, Inanc M, Isenberg DA. Animal models of the antiphospholipid syndrome. Rheumatology (Oxford) 1999;38:591–601.

    CrossRef  CAS  Google Scholar 

  40. Kita Y, Sumida T, Ichikawa K, et al. V gene analysis of anticardiolipin antibodies from MRL-lpr/lpr mice. J Immunol 1993;151:849–856.

    PubMed  CAS  Google Scholar 

  41. Kita Y, Sumida T, Iwamoto I,, et al. V gene analysis of anti-cardiolipin antibodies from (NZW x BXSB) F1 mice. Immunology 1994;82:494–501.

    PubMed  CAS  Google Scholar 

  42. Monestier M, et al. Monoclonal antibodies from NZW x BXSB F1 mice to beta2 glycoprotein I and cardiolipin. Species specificity and charge-dependent binding. J Immunol 1996;156:2631–2641.

    PubMed  CAS  Google Scholar 

  43. Foster MH, MacDonald M, Barrett KJ, et al. VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies. J Immunol 1991;147:1504–1511.

    PubMed  CAS  Google Scholar 

  44. Rahman A, Menon S, Latchman DS, et al. Sequences of monoclonal antiphospholipid antibodies: variations on an anti-DNA antibody theme. Semin Arthritis Rheum 1996;26:515–525.

    CrossRef  PubMed  CAS  Google Scholar 

  45. Dersimonian H, Schwartz RS, Barrett KJ, et al. Relationship of human variable region heavy chain germ-line genes to genes encoding anti-DNA autoantibodies. J Immunol 1987;139:2496–2501.

    PubMed  CAS  Google Scholar 

  46. Hoch S, Schwaber J. Identification and sequence of the VH gene elements encoding a human anti-DNA antibody. J Immunol 1987;139:1689–1693.

    PubMed  CAS  Google Scholar 

  47. Siminovitch KA, Misener V, Kwong PC, et al. A natural autoantibody is encoded by germline heavy and lambda light chain variable region genes without somatic mutation. J Clin Invest 1989;84:1675–1678.

    CrossRef  PubMed  CAS  Google Scholar 

  48. Cairns E, Kwong PC, Misener V, et al. Analysis of variable region genes encoding a human anti-DNA antibody of normal origin. Implications for the molecular basis of human autoimmune responses. J Immunol 1989;143:685–691.

    PubMed  CAS  Google Scholar 

  49. Logtenberg T, Young FM, Van Es JH, et al. Autoantibodies encoded by the most Jh-proximal human immunoglobulin heavy chain variable region gene. J Exp Med 1989;170:1347–1355.

    CrossRef  PubMed  CAS  Google Scholar 

  50. Rioux JD, Zdarsky E, Newkirk MM, et al. Anti-DNA and anti-platelet specificities of SLE-derived autoantibodies: evidence for CDR2H mutations and CDR3H motifs. Mol Immunol 1995;32:683–696.

    CrossRef  PubMed  CAS  Google Scholar 

  51. Hohmann A, Cairns E, Brisco M, et al. Immunoglobulin gene sequence analysis of anti-cardiolipin and anti-cardiolipin idiotype (H3) human monoclonal antibodies. Autoimmunity 1995;22:49–58.

    PubMed  CAS  Google Scholar 

  52. Siminovitch KA, Misener V, Kwong PC, et al. A human anti-cardiolipin autoantibody is encoded by developementally restricted heavy and light chain variable region genes. Autoimmunity 1990;8:97–105.

    PubMed  CAS  Google Scholar 

  53. Mariette X, Levy Y, Dubreuil ML, et al. Characterization of a human monoclonal autoantibody directed to cardiolipin/beta 2 glycoprotein I produced by chronic lymphocytic leukaemia B cells. Clin Exp Immunol 1993;94:385–390.

    CrossRef  PubMed  CAS  Google Scholar 

  54. Harmer IJ, Loizou S, Thompson KM, et al. A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded. Arthritis Rheum 1995;38:1068–1076.

    PubMed  CAS  Google Scholar 

  55. Denomme GA, Mahmoudi M, Cairns E, et al. Immunoglobulin V region sequences of two human antiplatelet monoclonal autoantibodies derived from B cells of normal origin. J Autoimmun 1994;7:521–535.

    CrossRef  PubMed  CAS  Google Scholar 

  56. Demaison C, Ravirajan CT, Isenberg DA, et al. Analysis of variable region genes encoding anti-Sm and anti-cardiolipin antibodies from a systemic lupus erythematosus patient. Immunology 1995;86:487–494.

    PubMed  CAS  Google Scholar 

  57. Lai CJ, Rauch J, Cho CS, et al. Immunological and molecular analysis of three monoclonal lupus anticoagulant antibodies from a patient with systemic lupus erythematosus. J Autoimmun 1998;11:39–51.

    CrossRef  PubMed  CAS  Google Scholar 

  58. Gallart T, Benito C, Reverter JC, et al. True anti-anionic phospholipid immunoglobulin M antibodies can exert lupus anticoagulant activity. Br J Haematol 2002;116:875–886.

    CrossRef  PubMed  CAS  Google Scholar 

  59. Chukwuocha RU, Zhu M, Cho CS, et al. Molecular and genetic characterizations of five pathogenic and two non-pathogenic monoclonal antiphospholipid antibodies. Mol Immunol 2002;39:299–311.

    CrossRef  PubMed  CAS  Google Scholar 

  60. Pierangeli SS, Liu X, Espinola R, et al. Functional analyses of patient-derived IgG monoclonal anticardiolipin antibodies using in vivo thrombosis and in vivo microcirculation models. Thromb Haemost 2000;84:388–395.

    PubMed  CAS  Google Scholar 

  61. Lieby P, Poindron V, Roussi S, et al. Pathogenic antiphospholipid antibody: an antigen selected needle in a haystack. Blood 2004. Epub ahead of print.

    Google Scholar 

  62. Tomlinson IM, et al. VBASE: A database of human immunoglobulin variable region genes. Cambridge, UK: MRC Centre for Protein Engineering: 1998.

    Google Scholar 

  63. Van Es JH, Aanstoot H, Gmelig-Meyling FH, et al. A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene. J Immunol 1992;149:2234–2240.

    PubMed  Google Scholar 

  64. Menon S, Rahman MA, Ravirajan CT, et al. The production, binding characteristics and sequence analysis of four human IgG monoclonal antiphospholipid antibodies. J Autoimmun 1997;10:43–57.

    CrossRef  PubMed  CAS  Google Scholar 

  65. Chukwuocha RU, Hsiao ET, Shaw P, et al. Isolation, characterization and sequence analysis of five IgG monoclonal anti-beta 2-glycoprotein-1 and anti-prothrombin antigen-binding fragments generated by phage display. J Immunol 1999;163:4604–4611.

    PubMed  CAS  Google Scholar 

  66. Ikematsu W, Luan FL, La Rosa L, et al. Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c mice. Arthritis Rheum 1998;41:1026–1039.

    CrossRef  PubMed  CAS  Google Scholar 

  67. von Landenberg C, Lackner KJ, von Landenberg P, et al. Isolation and characterization of two human monoclonal anti-phospholipid IgG from patients with autoimmune disease. J Autoimmun 1999;13:215–223.

    CrossRef  Google Scholar 

  68. Ehrenstein MR, Longhurst CM, Latchman DS, et al. Serological and genetic characterization of a human monoclonal immunoglobulin G anti-DNA idiotype. J Clin Invest 1994;93:1787–1797.

    PubMed  CAS  Google Scholar 

  69. Lieby P, Soley A, Levallois H, et al. The clonal analysis of anticardiolipin antibodies in a single patient with primary antiphospholipid syndrome reveals an extreme antibody heterogeneity. Blood 2001;97:3820–3828.

    CrossRef  PubMed  CAS  Google Scholar 

  70. Corbett SJ, Tomlinson IM, Sonnhammer EL, et al. Sequence of the human immunoglobulin diversity (D) segment locus: a systematic analysis provides no evidence for the use of DIR segments, inverted D segments, “minor” D segments or D-D recombination. J Mol Biol 1997;270:587–597.

    CrossRef  PubMed  CAS  Google Scholar 

  71. Cox JP, Tomlinson IM, Winter G. A directory of human germ-line V kappa segments reveals a strong bias in their usage. Eur J Immunol 1994;24:827–836.

    PubMed  CAS  Google Scholar 

  72. Dorner T, Farner NL, Lipsky PE. Ig lambda and heavy chain gene usage in early untreated systemic lupus erythematosus suggests intensive B cell stimulation. J Immunol 1999;163:1027–1036.

    PubMed  CAS  Google Scholar 

  73. Muramatsu M, Kinoshita K, Fagarasan S, et al. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 2000;102:553–563.

    CrossRef  PubMed  CAS  Google Scholar 

  74. Giles IP, Isenberg DA, Latchman DS, et al. How do antiphospholipid antibodies bind beta2-glycoprotein I? Arthritis Rheum 2003;48:2111–2121.

    CrossRef  PubMed  CAS  Google Scholar 

  75. Rahman A, Haley J, Latchman DS. Molecular expression systems for anti-DNA antibodies-1. Lupus 2002;11:824–832.

    CrossRef  PubMed  CAS  Google Scholar 

  76. Bird RE, Hardman KD, Jacobson JW, et al. Single-chain antigen-binding proteins. Science 1988;242:423–426.

    PubMed  CAS  Google Scholar 

  77. Better M, Chang CP, Robinson RR, et al. Escherichia coli secretion of an active chimeric antibody fragment. Science 1988;240:1041–1043.

    PubMed  CAS  Google Scholar 

  78. Blank M, Waisman A, Mozes E, et al. Characteristics and pathogenic role of anti-beta2-glycoprotein I single-chain Fv domains: induction of experimental antiphospholipid syndrome. Int Immunol 1999;11:1917–1926.

    CrossRef  PubMed  CAS  Google Scholar 

  79. Cocca BA, Seal SN, D’Agnillo P, et al. Structural basis for autoantibody recognition of phosphatidylserine-beta 2 glycoprotein I and apoptotic cells. Proc Natl Acad Sci U S A 2001;98:13826–13831.

    CrossRef  PubMed  CAS  Google Scholar 

  80. Pereira B, Benedict CR, Le A, et al. Cardiolipin binding a light chain from lupus-prone mice. Biochemistry 1998;37:1430–1437.

    CrossRef  PubMed  CAS  Google Scholar 

  81. Pewzner-Jung Y, Simon T, Eilat D. Structural elements controlling anti-DNA antibody affinity and their relationship to anti-phosphorylcholine activity. J Immunol 1996;156:3065–3073.

    PubMed  CAS  Google Scholar 

  82. Kumar S, Kalsi J, Ravirajan CT, et al. Molecular cloning and expression of the Fabs of human autoantibodies in Escherichia coli. Determination of the heavy or light chain contribution to the anti-DNA/-cardiolipin activity of the Fab. J Biol Chem 2000;275:35129–35136.

    CrossRef  PubMed  CAS  Google Scholar 

  83. Kumar S, Kalsi J, Latchman DS, et al. Expression of the Fabs of human auto-antibodies in Escherichia coli: optimization and determination of their fine binding characteristics and cross-reactivity. J Mol Biol 2001;308:527–539.

    CrossRef  PubMed  CAS  Google Scholar 

  84. Kumar S, Nagl S, Kalsi JK, et al. Anti-cardiolipin/beta-2 glycoprotein activities co-exist on human anti-DNA antibody light chains. Mol Immunol 2003;40:517–530.

    CrossRef  PubMed  CAS  Google Scholar 

  85. Giles IP, Haley J, Nagl S, et al. Relative importance of different human aPL derived heavy and light chains in the binding of aPL to cardiolipin. Mol Immunol 2003;40:49–60.

    CrossRef  PubMed  CAS  Google Scholar 

  86. Zhu M, Olee T, Le DT, et al. Characterization of IgG monoclonal anti-cardiolipin/anti-beta2GP1 antibodies from two patients with antiphospholipid syndrome reveals three species of antibodies. Br J Haematol 1999;105:102–109.

    CrossRef  PubMed  CAS  Google Scholar 

  87. Shah NM, Khamashta MA, Atsumi T, et al. Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients. Lupus 1998;7:3–6.

    CrossRef  PubMed  CAS  Google Scholar 

  88. Schulman S, Svenungsson E, Granqvist S. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Duration of Anticoagulation Study Group. Am J Med 1998;104:332–338.

    CrossRef  PubMed  CAS  Google Scholar 

  89. Blank M, Shoenfeld Y, Cabilly S, et al. Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides. Proc Natl Acad Sci U S A 1999;96:5164–5168.

    CrossRef  PubMed  CAS  Google Scholar 

  90. 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.

    CrossRef  PubMed  CAS  Google Scholar 

  91. Horizon A, et al. Results of a randomised, placebo controlled, double blind phase 1/2 clinical trial (RCT) to assess the safety and tolerability of LJP 1082 in patients with antiphospholipid syndrome. Arthritis Rheum 2003;48:S364.

    Google Scholar 

  92. Radic MZ, Mackle J, Erikson J, et al. Residues that mediate DNA binding of autoimmune antibodies. J Immunol 1993;150:4966–4977.

    PubMed  CAS  Google Scholar 

  93. Rahman A, Haley J, Radway-Bright E, et al. The Importance of somatic mutations in the V(lambda) gene 2a2 in human monoclonal anti-DNA antibodies. J Mol Biol 2001;307:149–160.

    CrossRef  PubMed  CAS  Google Scholar 

  94. Katz JB, Limpanasithikul W, Diamond B. Mutational analysis of an autoantibody: differential binding and pathogenicity. J Exp Med 1994;180:925–932.

    CrossRef  PubMed  CAS  Google Scholar 

  95. Giles IP, Haley JD, Nagl S, et al. A systematic analysis of sequences of human antiphospholipid and anti-beta2-glycoprotein I antibodies: the importance of somatic mutations and certain sequence motifs. Semin Arthritis Rheum 2003;32:246–265.

    CrossRef  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Rheumatology, Department of Medicine, University College London, London, UK

    Ian P. Giles BSc, MBBS, MRCP, PhD, David A. Isenberg MD, MBBS, FRCP & Anisur Rahman MA, BM, BCh, MRCP, PhD

Authors
  1. Ian P. Giles BSc, MBBS, MRCP, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David A. Isenberg MD, MBBS, FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anisur Rahman MA, BM, BCh, MRCP, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Lupus Research Unit, St Thomas’ Hospital, London, UK

    M. A. Khamashta MD, FRCP, PhD (Deputy Head) (Deputy Head)

Rights and permissions

Reprints and Permissions

Copyright information

© 2006 Springer-Verlag London Limited

About this chapter

Cite this chapter

Giles, I.P., Isenberg, D.A., Rahman, A. (2006). Lessons from Sequence Analysis of Monoclonal Antiphospholipid Antibodies. In: Khamashta, M.A. (eds) Hughes Syndrome. Springer, London. https://doi.org/10.1007/1-84628-009-5_38

Download citation

  • DOI: https://doi.org/10.1007/1-84628-009-5_38

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-85233-873-2

  • Online ISBN: 978-1-84628-009-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

search

Navigation