Protective autoantibodies in the rheumatic diseases: Lessons for therapy

Nature Reviews Rheumatology

Volumn 9, Issue 5, 2013, Pages 291-300

  Silverman, Gregg J ^a   Vas, Jaya ^a   Grönwall, Caroline ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; CELL NUCLEUS ANTIGEN; CITRULLINE; COMPLEMENT COMPONENT C1Q; CYCLIC CITRULLINATED PEPTIDE ANTIBODY; GLUCOCORTICOID; IMMUNOGLOBULIN G; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G3; IMMUNOGLOBULIN M; INTERLEUKIN 12P70; INTERLEUKIN 17; INTERLEUKIN 6; MANNOSE BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE PHOSPHATASE 1; OXIDIZED LOW DENSITY LIPOPROTEIN; PATTERN RECOGNITION RECEPTOR; PROTEIN ARGININE DEIMINASE; RHEUMATOID FACTOR; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 9; TOLL LIKE RECEPTOR AGONIST; TUMOR NECROSIS FACTOR;

ADAPTIVE IMMUNITY; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ATHEROSCLEROSIS; AUTOIMMUNE DISEASE; CARDIOVASCULAR DISEASE; CELL DEATH; COMORBIDITY; CYTOKINE PRODUCTION; DISEASE ASSOCIATION; DISEASE DURATION; DISEASE PREDISPOSITION; DISEASE SEVERITY; HOST CELL; HOST RESISTANCE; HUMAN; IMMUNOGLOBULIN DEFICIENCY; INFECTION RESISTANCE; INNATE IMMUNITY; NEGATIVE FEEDBACK; NONHUMAN; OXIDATION; PATHOGENESIS; PATHOGENICITY; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN MODIFICATION; RECEPTOR UPREGULATION; REVIEW; RHEUMATIC DISEASE; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; TISSUE INJURY;

ANIMALS; AUTOANTIBODIES; HUMANS; IMMUNOGLOBULIN M; IMMUNOMODULATION; RHEUMATIC DISEASES;

EID: 84877629509     PISSN: 17594790     EISSN: 17594804     Source Type: Journal    
DOI: 10.1038/nrrheum.2013.30     Document Type: Review

References (120)

1. Galbraith, P. R.,Valberg, L. S. & Brown, M. Patterns of granulocyte kinetics in health, infection and in carcinoma. Blood 25, 683-692 (19656p
2. Botto, M. & Walport, M. J. C1q, autoimmunity and apoptosis. Immunobiology 205, 395-406 (20026p
3. Wickman, G., Julian, L. & Olson, M. F. How apoptotic cells aid in the removal of their own cold dead bodies. Cell Death Differ. 19, 735-742 (20126p
4. Miller, Y. I.et al. Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ. Res. 108, 235-248 (20116p
5. Chang, M. K.et al. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J. Exp. Med. 200, 1359-1370 (20046p
6. Fadok, V. A., Bratton, D. L., Frasch, S. C., Warner, M. L. & Henson, P. M. The role of phosphatidylserine in recognition of apoptotic cells by phagocytes. Cell Death Differ. 5, 551-562 (19986p
7. Morelli, A. E.et al. Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: Dependence on complement receptors and effect on cytokine production. Blood 101, 611-620 (20036p
8. Ip, W. K. & Lau, Y. L. Distinct maturation of, but not migration between, human monocyte-derived dendritic cells upon ingestion of apoptotic cells of early or late phases. J. Immunol. 173, 189-196 (20046p
9. Shaw, P. X., Goodyear, C. S., Chang, M. K., Witztum, J. L. & Silverman, G. J. The autoreactivity of anti-phosphorylcholine antibodies for atherosclerosis-associated neo-antigens and apoptotic cells. J. Immunol. 170, 6151-6157 (20036p
10. Chen, Y.,Park, Y. B., Patel, E. & Silverman, G. J. IgM antibodies to apoptosis-associated determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells. J. Immunol. 182, 6031-6043 (20096p
11. Chen, Y.et al. Regulation of dendritic cells and macrophages by an anti-apoptotic cell natural antibody that suppresses TLR responses and inhibits inflammatory arthritis. J. Immunol. 183, 1346-1359 (20096p
12. Elkon, K. & Casali, P. Nature and functions of autoantibodies. Nat. Clin. Pract. Rheumatol. 4, 491-498 (20086p
13. Lleo, A., Invernizzi, P., Gao, B., Podda, M. & Gershwin, M. E. Definition of human autoimmunity-autoantibodies versus autoimmune disease. Autoimmun. Rev. 9, A259-A266 (20106p
14. Marshak-Rothstein, A. & Rifkin, I. R. Immunologically active autoantigens: The role of Toll-like receptors in the development of chronic inflammatory disease. Annu. Rev. Immunol. 25, 419-441 (20076p
15. Ronnblom, L. & Pascual, V. The innate immune system in SLE: Type I interferons and dendritic cells. Lupus 17, 394-399 (20086p
16. Calin, A. The epidemiology of rheumatoid disease: past and present. Dis. Markers 4, 1-6 (19866p
17. Mannik, M. Rheumatoid factors in the pathogenesis of rheumatoid arthritis. J. Rheumatol. Suppl. 32, 46-49 (19926p
18. Dorner, T., Egerer, K., Feist, E. & Burmester, G. R. Rheumatoid factor revisited. Curr. Opin. Rheumatol. 16, 246-253 (20046p
19. Zvaifler, N. J. The immunopathology of joint inflammation in rheumatoid arthritis. Adv. Immunol. 16, 265-336 (19736p).
20. Wozniczko-Orlowska, G. & Milgrom, F. Collagen-anticollagen complexes in rheumatoid arthritis sera. Int. Arch. Allergy Appl. Immunol. 68, 28-34 (19826p
21. Brand, D. D., Kang, A. H. & Rosloniec, E. F. Immunopathogenesis of collagen arthritis. Springer Semin. Immunopathol. 25, 3-18 (20036p
22. Raptopoulou, A., Sidiropoulos, P., Katsouraki, M. & Boumpas, D. T. Anti-citrulline antibodies in the diagnosis and prognosis of rheumatoid arthritis: Evolving concepts. Crit. Rev. Clin. Lab. Sci. 44, 339-363 (20076p
23. Klareskog, L., Ronnelid, J., Lundberg, K., Padyukov, L. & Alfredsson, L. Immunity to citrullinated proteins in rheumatoid arthritis. Annu. Rev. Immunol. 26, 651-675 (20086p
24. Wegner, N.et al. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol. Rev. 233, 34-54 (20106p
25. Ravetch, J. V. & Bolland, S. IgG Fc receptors. Annu. Rev. Immunol. 19, 275-290 (20016p
26. Gui, T., Shimokado, A., Sun, Y., Akasaka, T. & Muragaki, Y. Diverse roles of macrophages in atherosclerosis: From inflammatory biology to biomarker discovery. Mediators Inflamm. 2012, 693083 (20126p
27. Janeway, C. A. J., Goodnow, C. C. & Medzhitov, R. Danger - pathogen on the premises! Immunological tolerance. Curr. Biol. 6, 519-522 (19966p
28. Boule, M. W.et al. Toll-like receptor 9dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes. J. Exp. Med. 199, 1631-1640 (20046p
29. Yasuda, K.et al. Murine dendritic cell type I IFN production induced by human IgG-RNA immune complexes is IFN regulatory factor (IRF)5 and IRF7 dependent and is required for IL6 production. J. Immunol. 178, 6876-6885 (20076p
30. Lovgren, T., Eloranta, M. L., Bave, U., Alm, G. V. & Ronnblom, L. Induction of interferon-α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 50, 1861-1872 (20046p
31. Leadbetter, E. A.et al. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416, 603-607 (20026p
32. Marshak-Rothstein, A. Toll-like receptors in systemic autoimmune disease. Nat. Rev. Immunol. 6, 823-835 (20066p
33. Lee, J H.et al. Interleukin 17 (IL17) increases the expression of Toll-like receptor2, 4, and 9 by increasing IL1β and IL6 production in autoimmune arthritis. J. Rheumatol. 36, 684-692 (20096p
34. Zhao, X.et al. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis. Arthritis Res. Ther. 10, R94 (20086p
35. Kuhn, K. A.et al. Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J. Clin. Invest. 116, 961-973 (20066p
36. Sokolove, J., Zhao, X., Chandra, P. E. & Robinson, W. H. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγ receptor. Arthritis Rheum. 63, 53-62 (20116p
37. Abdollahi-Roodsaz, S.et al. Inhibition of toll-like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis. Arthritis Rheum. 56, 2957-2967 (20076p
38. Lu, M. C.et al. Anti-citrullinated protein antibodies bind surface-expressed citrullinated Grp78 on monocyte/macrophages and stimulate tumor necrosis factor α production. Arthritis Rheum. 62, 1213-1223 (20106p
39. Harre, U.et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J. Clin. Invest. 122, 1791-1802 (20126p
40. Ehrenstein, M. R. & Notley, C. A. The importance of natural IgM: Scavenger, protector and regulator. Nat. Rev. Immunol. 778-786 (20106p
41. Ehrenstein, M. R., Cook, H. T. & Neuberger, M. S. Deficiency in serum immunoglobulin (Ig)M predisposes to development of IgG autoantibodies. J. Exp. Med. 191, 1253-1258 (20006p
42. Boes, M.et al. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc. Natl Acad. Sci. USA 97, 1184-1189 (20006p
43. Kantor, A. B. & Herzenberg, L. A. Origin of murine B cell lineages. Annu. Rev. Immunol. 11, 501-538 (19936p
44. Kabat, E. A. & Wu, T. T. Identical V region amino acid sequences and segments of sequences in antibodies of different specificities. Relative contributions of VH and VL genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites. J. Immunol. 147, 1709-1719 (19916p
45. Feeney, A. J. Lack of N regions in fetal and neonatal mouse immunoglobulin VDJ junctional sequences. J. Exp. Med. 172, 1377-1390 (19906p
46. Herzenberg, L. A., Baumgarth, N. & Wilshire, J. A. B1 cell origins and VH repertoire determination. Curr. Top. Microbiol. Immunol. 252, 3-13 (20006p
47. Hardy, R. R. & Hayakawa, K. Positive and negative selection of natural autoreactive B cells. Adv. Exp. Med. Biol. 750, 227-238 (20126p
48. Chou, M. Y.et al. Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J. Clin. Invest. 119, 1335-1349 (20096p
49. Subramaniam, K. S.et al. The absence of serum IgM enhances the susceptibility of mice to pulmonary challenge with Cryptococcus neoformans. J. Immunol. 184, 5755-5767 (20106p
50. Gobet, R., Cerny, A., Ruedi, E., Hengartner, H. & Zinkernagel, R. M. The role of antibodies in natural and acquired resistance of mice to vesicular stomatitis virus. Exp. Cell Biol. 56, 175-180 (19886p
51. Ochsenbein, A. F.et al. Control of early viral and bacterial distribution and disease by natural antibodies. Science 286, 2156-2159 (19996p
52. Boes, M.et al. Enhanced B1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM. J. Immunol. 160, 4776-4787 (19986p).
53. Baumgarth, N., Chen, J., Herman, O. C., Jager, G. C. & Herzenberg, L. A. The role of B1 and B2 cells in immune protection from influenza virus infection. Curr. Top. Microbiol. Immunol. 252, 163-169 (20006p
54. Alugupalli, K. R.et al. The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes. J. Immunol. 170, 3819-3827 (20036p
55. Choi, Y. S. & Baumgarth, N. Dual role for B1a cells in immunity to influenza virus infection. J. Exp. Med. 205, 3053-3064 (20086p
56. Cancro, M. P., Sigal, N. H. & Klinman, N. R. Differential expression of an equivalent clonotype among BALB/c and C57BL/6 mice. J. Exp. Med. 147, 1-12 (19786p
57. Satow, Y., Cohen, G. H., Padlan, E. A. & Davies, D. R. Phosphocholine binding immunoglobulin Fab McPC603. An Xray diffraction study at 2.7 Å. J. Mol. Biol. 190, 593-604 (19866p
58. Sigal, N. H., Pickard, A. R., Metcalf, E. S., Gearhart, P. J. & Klinman, N. R. Expression of phosphorylcholine-specific B cells during murine development. J. Exp. Med. 146, 933-948 (19776p
59. Masmoudi, H., Mota-Santos, T., Huetz, F., Coutinho, A. & Cazenave, P. A. All T15 Id-positive antibodies (but not the majority of VHT15+ antibodies) are produced by peritoneal CD5+ B lymphocytes. Int. Immunol. 2, 515-520 (19906p
60. McDaniel, L. S., Benjamin, W. H. J., Forman, C. & Briles, D. E. Blood clearance by anti-phosphocholine antibodies as a mechanism of protection in experimental pneumococcal bacteremia. J. Immunol. 133, 3308-3312 (19846p
61. Taki, S., Meiering, M. & Rajewsky, K. Targeted insertion of a variable region gene into the immunoglobulin heavy chain locus. Science 262, 1268-1271 (19936p
62. Sieckmann, D. G.et al. B cells from M167 μ κ transgenic mice fail to proliferate after stimulation with soluble anti-Ig antibodies. A model for antigen-induced B cell anergy. J. Immunol. 152, 4873-4883 (19946p
63. Kenny, J. J.et al. Autoreactive B cells escape clonal deletion by expressing multiple antigen receptors. J. Immunol. 164, 4111-4119 (20006p
64. Kenny, J. J.et al. Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: A model for T15-idiotype dominance. J. Exp. Med. 176, 1637-1643 (19926p
65. Griffin, D. O., Holodick, N. E. & Rothstein, T. L. Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+ CD27+ CD43+ CD70+. J. Exp. Med. 208, 67-80 (20116p
66. Sivri, A. & Hascelik, Z. IgM deficiency in systemic lupus erythematosus patients. Arthritis Rheum. 38, 1713 (19956p
67. Saiki, O.et al. Development of selective IgM deficiency in systemic lupus erythematosus patients with disease of long duration. Arthritis Rheum. 30, 1289-1292 (19876p
68. Perazzio, S. F., Salomao, R., Silva, N. P., CarneiroSampaio, M. & Andrade, L. E. Serial screening shows that 28% of systemic lupus erythematosus adult patients carry an underlying primary immunodeficiency [abstract 657]. Arthritis Rheum. 64, S284 (20126p
69. Silverman, G. J.et al. Genetic imprinting of autoantibody repertoires in SLE patients. Clin. Exp. Immunol. 153, 102-116 (20086p
70. Silverman, G. J. Regulatory natural autoantibodies to apoptotic cells: pallbearers and protectors. Arthritis Rheum 63, 597-602 (20116p
71. Kagan, V. E.et al. Oxidative lipidomics of apoptosis: Redox catalytic interactions of cytochrome c with cardiolipin and phosphatidylserine. Free Radic. Biol. Med. 37, 1963-1985 (20046p
72. Ogden, C. A.et al. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J. Exp. Med. 194, 781-795 (20016p
73. Matsushita, M.et al. Origin of the classical complement pathway: Lamprey orthologue of mammalian C1q acts as a lectin. Proc. Natl Acad. Sci. USA 101, 10127-10131 (20046p
74. Korb, L. C. & Ahearn, J. M. C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J. Immunol. 158, 4525-4528 (19976p
75. Steinberg, D.Parthasarathy, S., Carew, T. E., Khoo, J. C. & Witztum, J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N. Engl. J. Med. 320, 915-924 (19896p
76. Shaw, P. X.et al. Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J. Clin. Invest. 105, 1731-1740 (20006p
77. Binder, C. J.et al. Pneumococcal vaccination decreases atherosclerotic lesion formation: Molecular mimicry between oxidized LDL and Streptococcus pneumoniae. Nat. Med. 9, 736-743 (20036p
78. Lewis, M. J.et al. Immunoglobulin M is required for protection against atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 120, 417-426 (20096p
79. Reardon, C. A.et al. Autoantibodies to OxLDL fail to alter the clearance of injected OxLDL in apolipoprotein Edeficient mice. J. Lipid Res. 45, 1347-1354 (20046p
80. Steinman, R. M. The control of immunity and tolerance by dendritic cell. Pathol. Biol. (Paris) 51, 59-60 (20036p
81. Fadok V. A.et al. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF. J. Clin. Invest. 101, 890-898 (19986p
82. Ogden, C. A., Kowalewski, R., Peng, Y., Montenegro, V. Elkon, K. B. IgM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo. Autoimmunity 38, 259-264 (20056p
83. Quartier, P., Potter, P. K., Ehrenstein, M. R., Walport, M. J. & Botto, M. Predominant role of IgM-dependent activation of the classical pathway in the clearance of dying cells by murine bone marrow-derived macrophages in vitro. Eur. J. Immunol. 35, 252-260 (20056p
84. Hughey, C. T., Brewer, J. W., Colosia, A. D., Rosse, W. F. & Corley, R. B. Production of IgM hexamers by normal and autoimmune B cells: Implications for the physiologic role of hexameric IgM. J. Immunol. 161, 4091-4097 (19986p
85. Arnold, J. N., Dwek, R. A., Rudd, P. M. & Sim, R. B. Mannan binding lectin and its interaction with immunoglobulins in health and in disease. Immunol. Lett. 106, 103-110 (20066p
86. Fraser, D. A., Laust, A. K., Nelson, E. L. & Tenner, A. J. C1q differentially modulates phagocytosis and cytokine responses during ingestion of apoptotic cells by human monocytes, macrophages, and dendritic cells. J. Immunol. 183, 6175-6185 (20096p
87. Stuart, L. M., Takahashi, K., Shi, L., Savill, J. & Ezekowitz, R. A. Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype. J. Immunol. 174, 3220-3226 (20056p
88. Taylor, P. R.et al. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J. Exp. Med. 192, 359-366 (20006p
89. Vas, J., Gronwall, C., Marshak-Rothstein, A. & Silverman, G. J. Natural antibody to apoptotic cell membranes inhibits the proinflammatory properties of lupus autoantibody immune complexes. Arthritis Rheum. 64, 3388-3398 (20126p
90. Hammaker, D. & Firestein, G. S. "Go upstream, young man": Lessons learned from the p38 saga. Ann. Rheum. Dis. 69 (Suppl. 1), i77-i82 (20106p
91. Clark, A. R. MAP kinase phosphatase 1: A novel mediator of biological effects of glucocorticoids? J. Endocrinol. 178, 15-12 (20036p
92. Grönwall, C.et al. MAPK Phosphatase1 is required for regulatory natural autoantibody mediated inhibition of TLR responses Proc. Natl Acad. Sci. USA 109, 19745-19750 (20126p
93. Liu, Y., Shepherd, E. G. & Nelin, L. D. MAPK phosphatases - regulating the immune response. Nat. Rev. Immunol. 7, 202-212 (20076p
94. Terato, K.et al. Induction of arthritis with monoclonal antibodies to collagen. J. Immunol. 148, 2103-2108 (19926p
95. Trentham, D. E., Townes, A. S. & Kang, A. H. Autoimmunity to type II collagen an experimental model of arthritis. J. Exp. Med. 146, 857-868 (19776p
96. Kleinau, S., Martinsson, P. & Heyman, B. Induction and suppression of collagen-induced arthritis is dependent on distinct Fcγ receptors. J. Exp. Med. 191, 1611-1616 (20006p
97. Notley, C. A., Brown, M. A., Wright, G. P. & Ehrenstein, M. R. Natural IgM is required for suppression of inflammatory arthritis by apoptotic cells. J. Immunol. 186, 4967-4972 (20116p
98. Brown, M.,Schiffman, G. & Rittenberg, M. B. Subpopulations of antibodies to phosphocholine in human serum. J. Immunol. 132, 1323-1328 (19846p
99. Padilla, N. D., Ciurana, C., van Oers, J., Ogilvie, A. C. & Hack, C. E. Levels of natural IgM antibodies against phosphorylcholine in healthy individuals and in patients undergoing isolated limb perfusion. J. Immunol. Methods 293, 1-11 (20046p
100. de Faire, U.et al. Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: Effects on uptake of oxidized LDL in macrophages as a potential mechanism. J. Autoimmun. 34, 73-79 (20106p
101. Fiskesund, R.et al. Low levels of antibodies against phosphorylcholine predict development of stroke in a population-based study from northern Sweden. Stroke. 41, 607-612 (20106p
102. Svenungsson, E.et al. Risk factors for cardiovascular disease in systemic lupus erythematosus. Circulation 104, 1887-1893 (20016p
103. Su, J.et al. Natural antibodies against phosphorylcholine as potential protective factors in SLE. Rheumatology (Oxford) 47, 1144-1150 (20086p
104. Ajeganova, S., de Faire, U., Jogestrand, T., Frostegard, J. & Hafstrom, I. Carotid atherosclerosis, disease measures, oxidized low-density lipoproteins, and atheroprotective natural antibodies for cardiovascular disease in early rheumatoid arthritis - an inception cohort study. J. Rheumatol. 39, 1146-1154 (20126p
105. Gronwall, C.et al. IgM autoantibodies to distinct apoptosis-associated antigens correlate with protection from cardiovascular events and renal disease in patients with SLE. Clin. Immunol. 142, 390-398 (20126p
106. Mehrani, T. & Petri, M. A. IgM anti-β2 glycoprotein I is protective against lupus nephritis and renal damage in SLE. Arthritis Rheum. 38, 450-453 (20116p
107. Casali, P. & Schettino, E. W. Structure and function of natural antibodies. Curr. Top. Microbiol. Immunol. 210, 167-179 (19966p
108. Coutinho, A., Kazatchkine, M. D. & Avrameas, S. Natural autoantibodies. Curr. Opin. Immunol. 7, 812-818 (19956p
109. Czajkowsky, D. M. & Shao, Z. The human IgM pentamer is a mushroom-shaped molecule with a flexural bias. Proc. Natl Acad. Sci. USA 106, 14960-14965 (20096p
110. Liszewski, M. K., Fang, C. J. & Atkinson, J. P. Inhibiting complement activation on cells at the step of C3 cleavage. Vaccine 26 (Suppl. 8), i22-i27 (20086p
111. Tenner, A. J. Membrane receptors for soluble defense collagens. Curr. Opin. Immunol. 11, 34-41 (19996p
112. Zhang, M.et al. Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury. J. Immunol. 177, 4727-4734 (20066p
113. Warrington, A. E., Van Keulen, V., Pease, L. R. & Rodriguez, M. Naturally occurring antibodies as therapeutics for neurologic disease: can human monoclonal IgMs replace the limited resource IVIG? Adv. Exp. Med. Biol. 750, 44-55 (20126p
114. Nielen, M. M.et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: A study of serial measurements in blood donors. Arthritis Rheum. 50, 380-386 (20046p
115. van de Stadt, L. A.et al. The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia. Ann. Rheum. Dis. 70, 128-133 (20116p
116. Deane, K. D., Norris, J. M. & Holers, V. M. Preclinical rheumatoid arthritis: Identification, evaluation, and future directions for investigation. Rheum. Dis. Clin. North Am. 36, 213-241 (20106p
117. Klareskog, L.et al. What precedes development of rheumatoid arthritis? Ann. Rheum. Dis. 63 (Suppl. 2), ii28-ii31 (20046p
118. Holers, V. M. Antibodies to citrullinated proteins: pathogenic and diagnostic significance. Curr. Rheumatol. Rep. 9, 396-400 (20076p
119. Binder, C. J. & Silverman, G. J. Natural antibodies and the autoimmunity of atherosclerosis. Springer Semin. Immunopathol. 26, 385-404 (20056p
120. Kaveri, S. V., Silverman, G. J. & Bayry, J. Natural IgM in immune equilibrium and harnessing their therapeutic potential. J. Immunol. 188, 939-945 (20126p