Structure–function analysis and the molecular origins of anti-DNA antibodies in systemic lupus erythematosus

Expert Reviews in Molecular Medicine

Volumn 1, Issue 7, 1999, Pages 1-28

  Isenberg, David A ^a   Kalsi, Jatinderpal ^a   Ravirajan, Chelliah T ^a   Rahman, Anisur ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

anti DNA antibodies; antibody; autoimmunity; dsDNA; lupus; molecular mimicry; recombinant immunoglobulin; SLE; ssDNA; structure function analysis; systemic lupus erythematosus

Indexed keywords

EID: 85012503300     PISSN: 14623994     EISSN: 14623994     Source Type: Journal    
DOI: 10.1017/S1462399499000423     Document Type: Article

References (108)

1. Duncan, R. and McConkey, E.H. (1982) How many proteins are there in a typical mammalian cell? Clin Chem 28, 749–755, PubMed ID:82184799
2. Gharavi, A.E., Chu, J.L. and Elkon, K.B. (1988) Autoantibodies to intracellular proteins in human systemic lupus erythematosus are not due to random polyclonal B cell activation. Arthritis Rheum 31, 1337–1345, PubMed ID:89050351
3. Isenberg, D.A. et al. (1997) The role of antibodies to DNA in systemic lupus erythematosus-a review and introduction to an international workshop on DNA antibodies held in London, May 1996. Lupus 6, 290–304, PubMed ID:97439375
4. Spronk, P.E., Limburg, P.C. and Kallenberg, C.G. (1995) Serological markers of disease activity in systemic lupus erythematosus. Lupus 4, 86–94, PubMed ID:95315972
5. Swaak, A.J. et al. (1979) Anti-dsDNA and complement profiles as prognostic guides in systemic lupus erythematosus. Arthritis Rheum 22, 226–235, PubMed ID:79124265
6. Lloyd, W. and Schur, P.H. (1981) Immune complexes, complement, and anti-DNA in exacerbations of systemic lupus erythematosus (SLE). Medicine (Baltimore) 60, 208–217, PubMed ID:81196769
7. ter Borg, E.J. et al. (1990) Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study. Arthritis Rheum 33, 634–643, PubMed ID:90267539
8. Okamura, M. et al. (1993) Significance of enzyme linked immunosorbent assay (ELISA) for antibodies to double stranded and single stranded DNA in patients with lupus nephritis: correlation with severity of renal histology. Ann Rheum Dis 52, 14–20, PubMed ID:93151657
9. Bootsma, H. et al. (1995) Prevention of relapses in systemic lupus erythematosus [published erratum appears in Lancet 1995 Aug 19;346(8973):516]. Lancet 345, 1595–1599, PubMed ID:95302858
10. Hay, E.M. et al. (1993) The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 86, 447–458, PubMed ID:94022887
11. Isenberg, D.A. et al. (1997) Long-term follow-up of autoantibody profiles in black female lupus patients and clinical comparison with Caucasian and Asian patients. Br J Rheumatol 36, 229–233, PubMed ID:97279495
12. Koffler, D., Schur, P.H. and Kunkel, H.G. (1967) Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med 126, 607–624, PubMed ID:68017474
13. Isenberg, D.A. et al. (1985) Detection of cross-reactive anti-DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives. Arthritis Rheum 28, 999–1007, PubMed ID:85307142
14. Andrzejewski, C., Jr. et al. (1981) Antigen-binding diversity and idiotypic cross-reactions among hybridoma autoantibodies to DNA. J Immunol 126, 226–231, PubMed ID:81095046
15. Andrews, B.S. et al. (1978) Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med 148, 1198–1215, PubMed ID:79069001
16. Schiffenbauer, J. et al. (1989) A unique sequence of the NZW I-E beta chain and its possible contribution to autoimmunity in the (NZB x NZW)F1 mouse. J Exp Med 170, 971–984, PubMed ID:89361262
17. Watanabe-Fukunaga, R. et al. (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356, 314–317, PubMed ID:92195401
18. Nagata, S. and Suda, T. (1995) Fas and Fas ligand: lpr and gld mutations. Immunol Today 16, 39–43, PubMed ID:95186001
19. Cohen, P.L. and Eisenberg, R.A. (1991) Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9, 243–269, PubMed ID:92000503
20. Ravirajan, C.T. et al. (1996) An analysis of apoptosis in lymphoid organs and lupus disease in murine systemic lupus erythematosus (SLE). Clin Exp Immunol 105, 306–312, PubMed ID:96332568
21. Steinberg, A.D. (1994) MRL-lpr/lpr disease: theories meet Fas. Semin Immunol 6, 55–69, PubMed ID:94220657
22. Rozzo, S.J. et al. (1994) Development of the T cell receptor repertoire in lpr mice. Semin Immunol 6, 19–26, PubMed ID:94220651
23. Eisenberg, R.A. et al. (1994) The role of B cell abnormalities in the systemic autoimmune syndromes of lpr and gld mice. Semin Immunol 6, 49–54, PubMed ID:94220656
24. Ray, S. and Diamond, B. (1994) Generation of a fusion partner to sample the repertoire of splenic B cells destined for apoptosis. Proc Natl Acad Sci U S A 91, 5548–5551, PubMed ID:94261623
25. Wofsy, D. and Seaman, W.E. (1987) Reversal of advanced murine lupus in NZB/NZW F1 mice by treatment with monoclonal antibody to L3T4. J Immunol 138, 3247–3253, PubMed ID:87196337
26. Datta, S.K. et al. (1991) Pathogenic anti-DNA autoantibodies and pathogenic autoantibody-inducing T cells. Immunol Ser 55, 133–153, PubMed ID:92062768
27. Mohan, C. et al. (1995) Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis. J Immunol 154, 1470–1480, PubMed ID:95123100
28. Ishida, H. et al. (1994) Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 179, 305–310, PubMed ID:94095937
29. Mihara, M. et al. (1998) IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W F1 mice. Clin Exp Immunol 112, 397–402, PubMed ID:98311541
30. Morrow, W.J.W. et al. (1998) Autoimmune Rheumatic Disease (2nd edn), Oxford University Press, Oxford
31. Stollar, B.D. (1986) Antibodies to DNA. CRC Crit Rev Biochem 20, 1–36, PubMed ID:86163298
32. Rauch, J. et al. (1984) Monoclonal anti-cardiolipin antibodies bind to DNA. Eur J Immunol 14, 529–534, PubMed ID:84236399
33. Isenberg, D.A. et al. (1994) The origin, sequence, structure, and consequences of developing anti- DNA antibodies. A human perspective. Arthritis Rheum 37, 169–180, PubMed ID:94175956
34. Gilkeson, G.S. et al. (1989) Induction of anti-double stranded DNA antibodies in normal mice by immunization with bacterial DNA. J Immunol 142, 1482–1486, PubMed ID:89140332
35. Gilkeson, G.S. et al. (1993) Molecular characterization of anti-DNA antibodies induced in normal mice by immunization with bacterial DNA. Differences from spontaneous anti-DNA in the content and location of VH CDR3 arginines. J Immunol 151, 1353–1364, PubMed ID:93329115
36. Rekvig, O.P. et al. (1995) Molecular analyses of anti-DNA antibodies induced by polyomavirus BK in BALB/c mice [published erratum appears in Scand J Immunol 1995 Aug;42(2):286].
37. Scand J Immunol 41, 593–602, PubMed ID:95288590
38. Fredriksen, K. et al. (1994) On the biological origin of anti-double-stranded (ds) DNA antibodies: systemic lupus erythematosus-related anti-dsDNA antibodies are induced by polyomavirus BK in lupus-prone (NZBxNZW) F1 hybrids, but not in normal mice. Eur J Immunol 24, 66–70, PubMed ID:94291743
39. Moens, U. et al. (1995) In vivo expression of a single viral DNA-binding protein generates systemic lupus erythematosus-related autoimmunity to double-stranded DNA and histones. Proc Natl Acad Sci U S A 92, 12393–12397, PubMed ID:96109273
40. Schwartz, L.M. and Osborne, B.A. (1993) Programmed cell death, apoptosis and killer genes. Immunol Today 14, 582–590, PubMed ID:94137360
41. Bell, D.A., Morrison, B. and VandenBygaart, P.(1990) Immunogenic DNA-related factors. Nucleosomes spontaneously released from normal murine lymphoid cells stimulate proliferation and immunoglobulin synthesis of normal mouse lymphocytes. J Clin Invest 85, 1487–1496, PubMed ID:90237226
42. Burlingame, R.W. et al. (1993) Genesis and evolution of antichromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen. J Clin Invest 91, 1687–1696, PubMed ID:93232296
43. Amoura, Z. et al. (1994) Nucleosome-restricted antibodies are detected before anti-dsDNA and/ or antihistone antibodies in serum of MRL-Mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria. Arthritis Rheum 37, 1684–1688, PubMed ID:95071547
44. Mohan, C. et al. (1993) Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus. J Exp Med 177, 1367–1381, PubMed ID:93240117
45. Ehrenstein, M., Longhurst, C. and Isenberg, D.A. (1993) Production and analysis of IgG monoclonal anti-DNA antibodies from systemic lupus erythematosus (SLE) patients. Clin Exp Immunol 92, 39–45, PubMed ID:93223313
46. Ehrenstein, M.R. et al. (1995) Human IgG anti-DNA antibodies deposit in kidneys and induce proteinuria in SCID mice. Kidney Int 48, 705–711, PubMed ID:96039495
47. Ravirajan, C.T. et al. (1998) Genetic, structural and functional properties of an IgG DNA-binding monoclonal antibody from a lupus patient with nephritis. Eur J Immunol 28, 339–350, PubMed ID:98143755
48. Gilkeson, G.S., Pritchard, A.J. and Pisetsky, D.S. (1991) Specificity of anti-DNA antibodies induced in normal mice by immunization with bacterial DNA. Clin Immunol Immunopathol 59, 288–300, PubMed ID:91183697
49. Atanassov, C. et al. (1991) New Zealand white rabbits immunized with RNA-complexed total histones develop an autoimmune-like response. Clin Exp Immunol 86, 124–133, PubMed ID:92006244
50. Ravirajan, C.T. et al. (1995) Effect of histone and histone-RNA complexes on the disease process of murine systemic lupus erythematosus. Autoimmunity 21, 117–122, PubMed ID:96274296
51. Desai, D.D. et al. (1993) Antigen-specific induction of antibodies against native mammalian DNA in nonautoimmune mice. J Immunol 151, 1614–1626, PubMed ID:93329143
52. Limpanasithikul, W., Ray, S. and Diamond, B. (1995) Cross-reactive antibodies have both protective and pathogenic potential. J Immunol 155, 967–973, PubMed ID:95332756
53. Putterman, C. et al. (1996) The double edged sword of the immune response: mutational analysis of a murine anti-pneumococcal, anti-DNA antibody. J Clin Invest 97, 2251–2259, PubMed ID:96217587
54. Stetler, D.A. and Jacob, S.T. (1985) Immunization of rabbits with purified RNA polymerase I induces a distinct population of antibodies against nucleic acids as well as anti- RNA polymerase I antibodies, both characteristic of systemic lupus erythematosus. Proc Natl Acad Sci U S A 82, 6797–6801, PubMed ID:86016786
55. James, S.P. (1991) Measurement of basic immunologic characteristics of human mononuclear cells. In Current Protocols in Immunology (Coligan, J.E. et al., eds), Green Publishing Company and Wiley-Interscience, New York
56. Mason, L.J., Timothy, L.M., Isenberg, D.A. and Kalsi, J. (in press) Immunisation with a peptide of SMB/B’ results in limited epitope spreading but not autoimmune disease. J Immunol
57. Gordon, C. et al. (1990) Measurement of antibodies to human DNA denatured by reactive oxygen species provides a new and more sensitive test for the diagnosis of SLE (abstract). Br J Rheum 39, S42
58. Rose, L.M., Latchman, D.S. and Isenberg, D.A. (1997) Apoptosis in peripheral lymphocytes in systemic lupus erythematosus: a review. Br J Rheumatol 36, 158–163, PubMed ID:97279480
59. Emlen, W., Niebur, J. and Kadera, R. (1994) Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol 152, 3685–3692, PubMed ID:94194130
60. Amzel, L.M. et al. (1974) The three dimensional structure of a combining region-ligand complex of immunoglobulin NEW at 3.5-Å resolution. Proc Natl Acad Sci U S A 71, 1427–1430, PubMed ID:74170844
61. Tonegawa, S. (1983) Somatic generation of antibody diversity. Nature 302, 575–581, PubMed ID:83167532
62. Cook, G.P. and Tomlinson, I.M. (1995) The human immunoglobulin VH repertoire. Immunol Today 16, 237–242, PubMed ID:95298183
63. Radic, M.Z. and Weigert, M. (1994) Genetic and structural evidence for antigen selection of anti-DNA antibodies. Annu Rev Immunol 12, 487–520, PubMed ID:94280777
64. Rahman, A., Latchman, D.S. and Isenberg, D.A. (1998) Immunoglobulin variable region sequences of human monoclonal anti-DNA antibodies. Seminars Arthritis Rheum 28, 141–154, PubMed ID:99087510
65. Shlomchik, M. et al. (1990) Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med 171, 265–292, PubMed ID:90111618
66. Tillman, D.M. et al. (1992) Both IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice. J Exp Med 176, 761–779, PubMed ID:92381444
67. Krishnan, M.R. and Marion, T.N. (1993) Structural similarity of antibody variable regions from immune and autoimmune anti-DNA antibodies. J Immunol 150, 4948–4957, PubMed ID:93267097
68. Waisman, A. and Mozes, E. (1993) Variable region sequences of autoantibodies from mice with experimental systemic lupus erythematosus. Eur J Immunol 23, 1566–1573, PubMed ID:93314700
69. Foster, M.H. et al. (1991) 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 147, 1504–1511, PubMed ID:91349568
70. Neuberger, M.S. and Milstein, C. (1995) Somatic hypermutation. Curr Opin Immunol 7, 248–254, PubMed ID:96053444
71. Huang, C. and Stollar, B.D. (1993) A majority of Ig H chain cDNA of normal human adult blood lymphocytes resembles cDNA for fetal Ig and natural autoantibodies. J Immunol 151, 5290–5300, PubMed ID:94044753
72. Shlomchik, M.J. et al. (1987) The role of clonal selection and somatic mutation in autoimmunity. Nature 328, 805–811, PubMed ID:87315336
73. Stevenson, F.K. et al. (1993) Utilization of the VH4–21 gene segment by anti-DNA antibodies from patients with systemic lupus erythematosus. J Autoimmun 6, 809–825, PubMed ID:94206428
74. Winkler, T.H., Fehr, H. and Kalden, J.R. (1992) Analysis of immunoglobulin variable region genes from human IgG anti- DNA hybridomas. Eur J Immunol 22, 1719–1728, PubMed ID:92324282
75. Longhurst, C. et al. (1996) Analysis of immunoglobulin variable region genes of a human IgM anti- myeloperoxidase antibody derived from a patient with vasculitis. Immunology 87, 334–338, PubMed ID:96245990
76. Cairns, E. et al. (1989) 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 143, 685–691, PubMed ID:89292695
77. Radic, M.Z. et al. (1991) Ig H and L chain contributions to autoimmune specificities. J Immunol 146, 176–182, PubMed ID:91079543
78. Radic, M.Z. et al. (1993) Residues that mediate DNA binding of autoimmune antibodies. J Immunol 150, 4966–4977, PubMed ID:93267099
79. Pewzner-Jung, Y., Simon, T. and Eilat, D. (1996) Structural elements controlling anti-DNA antibody affinity and their relationship to anti-phosphorylcholine activity. J Immunol 156, 3065–3073, PubMed ID:96183266
80. Katz, J.B., Limpanasithikul, W. and Diamond, B. (1994) Mutational analysis of an autoantibody: differential binding and pathogenicity. J Exp Med 180, 925–932, PubMed ID:94342852
81. Polymenis, M. and Stollar, B.D. (1994) Critical binding site amino acids of anti-Z-DNA single chain Fv molecules. Role of heavy and light chain CDR3 and relationship to autoantibody activity. J Immunol 152, 5318–5329, PubMed ID:94246172
82. Barbas, S.M. et al. (1995) Human autoantibody recognition of DNA. Proc Natl Acad Sci U S A 92, 2529–2533, PubMed ID:95223974
83. Roben, P. et al. (1996) Repertoire cloning of lupus anti-DNA autoantibodies. J Clin Invest 98, 2827–2837, PubMed ID:97136530
84. Mockridge, C.I. et al. (1996) Use of phage surface expression to analyze regions of human V4–34(VH4- 21)-encoded IgG autoantibody required for recognition of DNA: no involvement of the 9G4 idiotope. J Immunol 157, 2449–2454, PubMed ID:96399073
85. Rahman, M.A.A. et al. (1998) Properties of whole human IgG molecules produced by the expression of cloned anti-DNA antibody cDNA in mammalian cells. J Autoimmun 11, 661–669, PubMed ID:99096528
86. Ohnishi, K. et al. (1994) Comparison of pathogenic and non-pathogenic murine antibodies to DNA: antigen binding and structural characteristics. Int Immunol 6, 817–830, PubMed ID:94368748
87. Kalsi, J.K. et al. (1996) Functional and modelling studies of the binding of human monoclonal anti-DNA antibodies to DNA. Mol Immunol 33, 471–483, PubMed ID:96265196
88. Burlingame, R.W. et al. (1994) The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus. J Clin Invest 94, 184–192, PubMed ID:94314893
89. Swanson, P.C. et al. (1996) Ligand recognition by murine anti-DNA autoantibodies. II. Genetic analysis and pathogenicity. J Clin Invest 97, 1748–1760, PubMed ID:96181576
90. Vlahakos, D. et al. (1992) Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo. J Am Soc Nephrol 2, 1345–1354, PubMed ID:92329701
91. Gibson, A.L. et al. (1985) Crystallographic characterization of the Fab fragment of a monoclonal anti-ss-DNA antibody. Mol Immunol 22, 499–502, PubMed ID:85296009
92. Cygler, M. et al. (1987) Crystallization and structure determination of an autoimmune anti-poly(dT) immunoglobulin Fab fragment at 3.0 Å resolution. J Biol Chem 262, 643–648, PubMed ID:87109158
93. Mol, C.D. et al. (1994) Structure of an immunoglobulin Fab fragment specific for triple-stranded DNA. J Biol Chem 269, 3615–3622, PubMed ID:94148866
94. Mol, C.D. et al. (1994) Structure of an immunoglobulin Fab fragment specific for poly(dG).poly(dC). J Biol Chem 269, 3605–3614, PubMed ID:94148865
95. Isenberg, D. et al. (1997) Anti-DNA antibodies: from gene usage to crystal structures. Immunol Today 18, 149–153, PubMed ID:97282202
96. Bernstein, F.C. et al. (1977) The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 112, 535–542, PubMed ID:77209992
97. Martin, A.C., Cheetham, J.C. and Rees, A.R. (1991) Molecular modeling of antibody combining sites. Methods Enzymol 203, 121–153, PubMed ID:92107062
98. Chothia, C. et al. (1989) Conformations of immunoglobulin hypervariable regions. Nature 342, 877–883, PubMed ID:90081868
99. Chothia, C. et al. (1992) Structural repertoire of the human VH segments. J Mol Biol 227, 799–817, PubMed ID:93021118
100. Martin, A.C. and Thornton, J.M. (1996) Structural families in loops of homologous proteins: automatic classification, modelling and application to antibodies. J Mol Biol 263, 800–815, PubMed ID:97103205
101. Martin, A.C., Cheetham, J.C. and Rees, A.R. (1989) Modeling antibody hypervariable loops: a combined algorithm. Proc Natl Acad Sci U S A 86, 9268–9272, PubMed ID:90083249
102. Eilat, D., Webster, D.M. and Rees, A.R. (1988) V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice. J Immunol 141, 1745–1753, PubMed ID:88315787
103. Stollar, B.D., Zon, G. and Pastor, R.W. (1986) A recognition site on synthetic helical oligonucleotides for monoclonal anti-native DNA autoantibody. Proc Natl Acad Sci U S A 83, 4469–4473, PubMed ID:86233448
104. Eagan, M.A. et al. (1995) Structural patterns in anti-DNA autoantibodies: A molecular modelling study. Bioorgan Chem 23, 482–498
105. Barry, M.M. et al. (1994) Sequencing and modeling of anti-DNA immunoglobulin Fv domains. Comparison with crystal structures. J Biol Chem 269, 3623–3632, PubMed ID:94148867
106. Miyazaki, S. et al. (1997) Is structural flexibility of antigen-binding loops involved in the affinity maturation of anti-DNA antibodies? Int Immunol 9, 771–777, PubMed ID:97328385
107. Isenberg, D.A. and Horsfall, A. (1998) Systemic lupus erythematosis in adults. In Oxford Textbook of Rheumatology (2nd edn) (Maddison, P.J. et al., eds), pp. 1145–1180, Oxford University Press
108. Lafer, E.M. et al. (1981) Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids. J Exp Med 153, 897–909, PubMed ID:81241321