Skip to main content
Download PDF

Protective molecules and their cognate antibodies: new players in autoimmunity

Autoimmunity Highlights volume 1, pages 63–72 (2010)Cite this article

Abstract

Impairment of the clearance of apoptotic material seems to contribute to autoantigen exposure, which can initiate or maintain an autoimmune response in predisposed individuals. Complement component C1q, Creactive protein (CRP), serum amyloid P (SAP), mannose-binding lectin (MBL), apolipoprotein A-1 (Apo A-1) and long pentraxin 3 (PTX3) are molecules involved in the removal of apoptotic bodies and pathogens, and in other antiinflammatory pathways. For this reason they have been called “protective” molecules. C1q has a key role in the activation of the complement cascade and acts as a bridging molecule between apoptotic bodies and macrophages favouring phagocytosis. In addition to other functions, CRP, SAP and MBL bind to the surface of numerous pathogens as well as cellular debris and activate the complement cascade, thus stimulating their clearance by immune cells. The role of PTX3 is more controversial. In fact, PTX also promotes the clearance of microorganisms, but the activation of the complement cascade through C1q and removal of apoptotic material can be either stimulated or inhibited by this molecule. Antibodies against protective molecules have been recently reported in systemic lupus erythematosus and other autoimmune rheumatic diseases. Some of them seem to be pathogenetic and others protective. Thus, protective molecules and their cognate antibodies may constitute a regulatory network involved in autoimmunity. Dysregulation of this system might contribute to the development of autoimmune diseases in predisposed individuals.

References

  1. 1.

    Janko C, Schorn C, Grossmayer GE et al (2008) Inflammatory clearance of apoptotic remnants in systemic lupus erythematosus (SLE). Autoimmun Rev 8:9–12

    PubMed  Google Scholar 

  2. 2.

    Coleman ML, Sahai EA, Yeo M et al (2001) Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol 3(4):339–345

    PubMed  Google Scholar 

  3. 3.

    McPhillips KA, Erwig LP (2009) Assessment of apoptotic cell phagocytosis by macrophages. Methods Mol Biol 559:247–256

    PubMed  Google Scholar 

  4. 4.

    Sontheimer RD, Racila E, Racila DM (2005) C1q: its functions within the innate and adaptive immune responses and its role in lupus autoimmunity. J Invest Dermatol 125(1):14–23

    PubMed  Google Scholar 

  5. 5.

    Païdassi H, Tacnet-Delorme P, Garlatti V et al (2008) C1q binds to phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition. J Immunol 180(4):2329–2338

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    van de Wetering JK, van Golde LM, Batenburg JJ (2004) Collectins: players of the innate immune system. Eur J Biochem 271(7):1229–1249

    PubMed  Google Scholar 

  7. 7.

    Ahmed AE, Veitch J, Whaley K (1990) Mechanism of action of an inhibitor of complement-mediated prevention of immune precipitation. Immunology 70(2):139–144

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Botto M (1998) C1q knock-out mice for the study of complement deficiency in autoimmune disease. Exp Clin Immunogenet 15(4):231–234

    PubMed  Google Scholar 

  9. 9.

    Botto M, Dell’Agnola C, Bygrave AE et al (1998) Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 19(1):56–59

    PubMed  Google Scholar 

  10. 10.

    Marto N, Bertolaccini ML, Calabuig E et al (2005) Anti-C1q antibodies in nephritis: correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus. Ann Rheum Dis 64(3):444–448

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Bijl M, Reefman E, Horst G et al (2006) Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement. Ann Rheum Dis 65(1):57–63

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Sinico RA, Radice A, Ikehata M et al (2005) Anti-C1q autoantibodies in lupus nephritis: prevalence and clinical significance. Ann N Y Acad Sci 1050:193–200

    PubMed  Google Scholar 

  13. 13.

    Trendelenburg M (2005) Antibodies against C1q in patients with systemic lupus erythematosus. Springer Semin Immunopathol 27(3):276–285

    PubMed  Google Scholar 

  14. 14.

    Moroni G, Radice A, Giammarresi G et al (2009) Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis. Ann Rheum Dis 68(2):234–237

    PubMed  Google Scholar 

  15. 15.

    Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111(12):1805–1812

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Szyper Kravitz M, Shoenfeld Y (2006) Autoimmunity to protective molecules: is it the perpetuum mobile (vicious cycle) of autoimmune rheumatic diseases? Nat Clin Pract Rheumatol 2:481–490

    Google Scholar 

  17. 17.

    Szyper Kravitz M, Pitashny M, Shoenfeld Y (2005) Protective molecules — C-reactive protein (CRP), serum amyloid P (SAP), pentraxin3 (PTX3), mannose-binding lectin (MBL), and apolipoprotein A1 (Apo A1), and their autoantibodies: prevalence and clinical significance in autoimmunity. J Clin Immunol 25:582–591

    Google Scholar 

  18. 18.

    Castrejón I, Ortiz AM, García-Vicuña R et al (2008) Are the Creactive protein values and erythrocyte sedimentation rate equivalent when estimating the 28-joint disease activity score in rheumatoid arthritis? Clin Exp Rheumatol 26(5):769–775

    PubMed  Google Scholar 

  19. 19.

    Szalai AJ (2002) The antimicrobial activity of C-reactive protein. Microbes Infect 4(2):201–205

    PubMed  Google Scholar 

  20. 20.

    Kindmark CO (1971) Stimulating effect of C-reactive protein on phagocytosis of various species of pathogenic bacteria. Clin Exp Immunol 8(6):941–948

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Bharadwaj D, Mold C, Markham E et al (2001) Serum amyloid P component binds to Fc gamma receptors and opsonizes particles for phagocytosis. J Immunol 166(11):6735–6741

    PubMed  Google Scholar 

  22. 22.

    Mold C, Baca R, Du Clos TW (2002) Serum amyloid P component and C-reactive protein opsonize apoptotic cells for phagocytosis through Fcgamma receptors. J Autoimmun 19(3):147–154

    PubMed  Google Scholar 

  23. 23.

    Gershov D, Kim S, Brot N et al (2000) C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 192(9):1353–1364

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Ridker PM, Paynter NP, Rifai N et al (2008) C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men. Circulation 118(22):2243–2251

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Bucova M, Bernadic M, Buckingham T (2008) C-reactive protein, cytokines and inflammation in cardiovascular diseases. Bratisl Lek Listy 109(8):333–340

    PubMed  Google Scholar 

  26. 26.

    Aukrust P, Halvorsen B, Yndestad A et al (2008) Chemokines and cardiovascular risk. Arterioscler Thromb Vasc Biol 28(11):1909–1919

    PubMed  Google Scholar 

  27. 27.

    Gonzalez-Gay MA, Llorca J, Garcia-Unzueta MT et al (2008) High-grade inflammation, circulating adiponectin concentrations and cardiovascular risk factors in severe rheumatoid arthritis. Clin Exp Rheumatol 26(4):596–603

    PubMed  Google Scholar 

  28. 28.

    Bultink IE, Turkstra F, Diamant M et al (2008) Prevalence of and risk factors for the metabolic syndrome in women with systemic lupus erythematosus. Clin Exp Rheumatol 26(1):32–38

    PubMed  Google Scholar 

  29. 29.

    Taskinen S, Hyvönen M, Kovanen PT et al (2005) C-reactive protein binds to the 3beta-OH group of cholesterol in LDL particles. Biochem Biophys Res Commun 329(4):1208–1216

    PubMed  Google Scholar 

  30. 30.

    Du Clos TW, Mold C (2004) C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res 30(3):261–277

    PubMed  Google Scholar 

  31. 31.

    Singh U, Dasu MR, Yancey PG et al (2008) Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats. J Lipid Res 49(5):1015–1023

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Bhakdi S, Torzewski M, Paprotka K et al (2004) Possible protective role for C-reactive protein in atherogenesis: complement activation by modified lipoproteins halts before detrimental terminal sequence. Circulation 109(15):1870–1876

    PubMed  Google Scholar 

  33. 33.

    Khreiss T, Jozsef L, Potempa LA et al (2004) Conformational rearrangement in C-reactive protein is required for proinflammatory actions on human endothelial cells. Circulation 109(16):2016–2022

    PubMed  Google Scholar 

  34. 34.

    Schwedler SB, Amann K, Wernicke K et al (2005) Native Creactive protein increases whereas modified C-reactive protein reduces atherosclerosis in apolipoprotein E-knockout mice. Circulation 112(7):1016–1023

    PubMed  Google Scholar 

  35. 35.

    Bassi N, Zampieri S, Ghirardello A et al (2009) Pentraxins, antipentraxins antibodies, and atherosclerosis. Clin Rev Allerg Immunol 37(1):36–43

    Google Scholar 

  36. 36.

    Keenan RT, Swearingen CJ, Yazici Y (2008) Erythrocyte sedimentation rate and C-reactive protein levels are poorly correlated with clinical measures of disease activity in rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis patients. Clin Exp Rheumatol 26(5):814–819

    PubMed  Google Scholar 

  37. 37.

    Meyer O (2010) Anti-CRP antibodies in systemic lupus erythematosus. Joint Bone Spine. DOI: 10.1016/j.jbspin.2010.04.010

  38. 38.

    Wetterö J, Nilsson L, Jonasson L, Sjöwall C (2009) Reduced serum levels of autoantibodies against monomeric C-reactive protein (CRP) in patients with acute coronary syndrome. Clin Chim Acta 400(1–2):128–131

    PubMed  Google Scholar 

  39. 39.

    Sjöwall C, Bengtsson AA, Sturfelt G et al (2004) Serum levels of autoantibodies against monomeric C-reactive protein are correlated with disease activity in systemic lupus erythematosus. Arthritis Res Ther 6(2):R87–R94

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    O’Neill SG, Isenberg DA, Rahman A (2007) Could antibodies to C-reactive protein link inflammation and cardiovascular disease in patients with systemic lupus erythematosus? Ann Rheum Dis 66:989–991

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Valdivielso P, Gómez-Doblas JJ, Macias M et al (2008) Lupusassociated endothelial dysfunction, disease activity and arteriosclerosis. Clin Exp Rheumatol 26(5):827–833

    PubMed  Google Scholar 

  42. 42.

    Avalos I, Rho YH, Chung CP et al (2008) Atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Clin Exp Rheumatol 26(5 Suppl 51):S5–S13

    PubMed  Google Scholar 

  43. 43.

    Doria A, Sherer Y, Meroni PL et al (2005) Inflammation and accelerated atherosclerosis — basic mechanisms. Rheum Dis Clin N Am 31:329–354

    Google Scholar 

  44. 44.

    Doria A, Shoenfeld Y, Pauletto P (2004) Premature coronary disease in systemic lupus. N Engl J Med 350(15):1571–1575

    PubMed  Google Scholar 

  45. 45.

    Doria A, Shoenfeld Y, Wu R et al (2003) Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus. Ann Rheum Dis 62:1071–1077

    PubMed  PubMed Central  Google Scholar 

  46. 46.

    Doria A, Iaccarino L, Ghirardello A et al (2006) Long-term prognosis and causes of death in systemic lupus erythematosus. Am J Med 119:1497–1499

    Google Scholar 

  47. 47.

    Emsley J, White HE, O’Hara BP et al (1994) Structure of pentameric human serum amyloid P component. Nature 367(6461):338–345

    PubMed  Google Scholar 

  48. 48.

    Mold C, Gresham HD, Du Clos TW (2001) Serum amyloid P component and C-reactive protein mediate phagocytosis through murine Fc gamma Rs. J Immunol 166(2):1200–1205

    PubMed  Google Scholar 

  49. 49.

    Bickerstaff MC, Botto M, Hutchinson WL et al (1999) Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med 5(6):694–697

    PubMed  Google Scholar 

  50. 50.

    Zandman-Goddard G, Blank M, Langevitz P et al (2005) Antiserum amyloid component P antibodies in patients with systemic lupus erythematosus correlate with disease activity. Ann Rheum Dis 64(12):1698–1702

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    Saevarsdottir S, Vikingsdottir T, Valdimarsson H (2004) The potential role of mannan-binding lectin in the clearance of selfcomponents including immune complexes. Scand J Immunol 60(1–2):23–29

    PubMed  Google Scholar 

  52. 52.

    Avcin T, Canova M, Guilpain P et al (2008) Infections, connective tissue diseases and vasculitis. Clin Exp Rheumatol 26(1 Suppl 48):S18–S26

    PubMed  Google Scholar 

  53. 53.

    Ramos-Casals M, Brito-Zerón P, Soria N et al (2009) Mannosebinding lectin-low genotypes are associated with milder systemic and immunological disease expression in primary Sjögren’s syndrome. Rheumatology (Oxford) 48(1):65–69

    Google Scholar 

  54. 54.

    Gupta B, Raghav SK, Agrawal C et al (2006) Anti-MBL autoantibodies in patients with rheumatoid arthritis: prevalence and clinical significance. J Autoimmun 27(2):125–133

    PubMed  Google Scholar 

  55. 55.

    Saevarsdottir S, Vikingsdottir T, Vikingsson A et al (2001) Low mannose binding lectin predicts poor prognosis in patients with early rheumatoid arthritis. A prospective study. J Rheumatol 28(4):728–734

    PubMed  Google Scholar 

  56. 56.

    Ip WK, Lau YL, Chan SY et al (2000) Mannose-binding lectin and rheumatoid arthritis in southern Chinese. Arthritis Rheum 43(8):1679–1687

    PubMed  Google Scholar 

  57. 57.

    Graudal NA, Homann C, Madsen HO et al (1998) Mannan binding lectin in rheumatoid arthritis. A longitudinal study. J Rheumatol 25(4):629–635

    PubMed  Google Scholar 

  58. 58.

    Garred P, Madsen HO, Marquart H et al (2000) Two edged role of mannose binding lectin in rheumatoid arthritis: a cross sectional study. J Rheumatol 27(1):26–34

    PubMed  Google Scholar 

  59. 59.

    Jacobsen S, Madsen HO, Klarlund M et al (2001) The influence of mannose binding lectin polymorphisms on disease outcome in early polyarthritis. TIRA Group. J Rheumatol 28(5):935–942

    PubMed  Google Scholar 

  60. 60.

    Graudal NA, Madsen HO, Tarp U et al (2000) The association of variant mannose-binding lectin genotypes with radiographic outcome in rheumatoid arthritis. Arthritis Rheum 43(3):515–521

    PubMed  Google Scholar 

  61. 61.

    Font J, Ramos-Casals M, Brito-Zerón P et al (2007) Association of mannose-binding lectin gene polymorphisms with antiphospholipid syndrome, cardiovascular disease and chronic damage in patients with systemic lupus erythematosus. Rheumatology (Oxford) 46(1):76–80

    Google Scholar 

  62. 62.

    Lee YH, Witte T, Momot T et al (2005) The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a meta-analysis. Arthritis Rheum 52(12):3966–3974

    PubMed  Google Scholar 

  63. 63.

    Best LG, Ferrell RE, Decroo S et al (2009) Genetic and other factors determining mannose-binding lectin levels in American Indians: the Strong Heart Study. BMC Med Genet 10:5

    PubMed  PubMed Central  Google Scholar 

  64. 64.

    Hegele RA, Ban MR, Anderson CM et al (2000) Infectionsusceptibility alleles of mannose-binding lectin are associated with increased carotid plaque area. J Investig Med 48(3):198–202

    PubMed  Google Scholar 

  65. 65.

    Tsutsumi A, Takahashi R, Sumida T (2005) Mannose binding lectin: genetics and autoimmune disease. Autoimmun Rev 4(6):364–372

    PubMed  Google Scholar 

  66. 66.

    Øhlenschlaeger T, Garred P, Madsen HO et al (2004) Mannosebinding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med 351(3):260–267

    PubMed  Google Scholar 

  67. 67.

    Mok MY, Jack DL, Lau CS et al (2004) Antibodies to mannose binding lectin in patients with systemic lupus erythematosus. Lupus 13(7):522–528

    PubMed  Google Scholar 

  68. 68.

    Seelen MA, Trouw LA, van der Hoorn JW et al (2003) Autoantibodies against mannose-binding lectin in systemic lupus erythematosus. Clin Exp Immunol 134(2):335–343

    PubMed  PubMed Central  Google Scholar 

  69. 69.

    Van Craeyveld E, Lievens J, Jacobs F et al (2009) Apolipoprotein A-I and lecithin: cholesterol acyltransferase transfer induce cholesterol unloading in complex atherosclerotic lesions. Gene Ther 16(6):757–765

    PubMed  Google Scholar 

  70. 70.

    Mendez AJ (2010) The promise of apolipoprotein A-I mimetics. Curr Opin Endocrinol Diabetes Obes 17(2):171–176

    PubMed  Google Scholar 

  71. 71.

    Bailey D, Jahagidar R, Gordon A et al (2010) RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J Am Coll Cardiol 55(23):2580–2589

    PubMed  Google Scholar 

  72. 72.

    Papadakis JA, Sidiropoulos PI, Karvounaris SA et al (2009) High prevalence of metabolic syndrome and cardiovascular risk factors in men with ankylosing spondylitis on anti-TNFalpha treatment: correlation with disease activity. Clin Exp Rheumatol 27(2):292–298

    PubMed  Google Scholar 

  73. 73.

    Hyka N, Dayer JM, Modoux C et al (2001) Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes. Blood 97(8):2381–2389

    PubMed  Google Scholar 

  74. 74.

    Park YB, Lee SK, Lee WK et al (1999) Lipid profiles in untreated patients with rheumatoid arthritis. J Rheumatol 26(8):1701–1704

    PubMed  Google Scholar 

  75. 75.

    Doherty NS, Littman BH, Reilly K et al (1998) Analysis of changes in acute-phase plasma proteins in an acute inflammatory response and in rheumatoid arthritis using two-dimensional gel electrophoresis. Electrophoresis 19(2):355–363

    PubMed  Google Scholar 

  76. 76.

    Oliviero F, Sfriso P, Baldo G et al (2009) Apolipoprotein A-I and cholesterol in synovial fluid of patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis. Clin Exp Rheumatol 27(1):79–83

    PubMed  Google Scholar 

  77. 77.

    Burger D, Dayer JM (2002) High-density lipoprotein-associated apolipoprotein A-I: the missing link between infection and chronic inflammation? Autoimmun Rev 1(1–2):111–117

    PubMed  Google Scholar 

  78. 78.

    Batuca JR, Ames PR, Isenberg DA et al (2007) Antibodies toward high-density lipoprotein components inhibit paraoxonase activity in patients with systemic lupus erythematosus. Ann N Y Acad Sci 1108:137–146

    PubMed  Google Scholar 

  79. 79.

    O’Neill SG, Giles I, Lambrianides A et al (2010) Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus. Arthritis Rheum 62(3):845–854

    PubMed  Google Scholar 

  80. 80.

    Batuca JR, Ames PR, Amaral M et al (2009) Anti-atherogenic and anti-inflammatory properties of high-density lipoprotein are affected by specific antibodies in systemic lupus erythematosus. Rheumatology (Oxford) 48(1):26–31

    Google Scholar 

  81. 81.

    Ortega-Hernandez OD, Bassi N, Shoenfeld Y et al (2009) The long pentraxin 3 and its role in autoimmunity. Semin Arthritis Rheum 39(1):38–54

    PubMed  Google Scholar 

  82. 82.

    Mantovani A, Garlanda C, Doni A et al (2008) Pentraxins in innate immunity: from C-reactive protein to the long pentraxin PTX3. J Clin Immunol 28(1):1–13

    PubMed  Google Scholar 

  83. 83.

    Nauta AJ, Bottazzi B, Mantovani A et al (2003) Biochemical and functional characterization of the interaction between pentraxin3 and C1q. Eur J Immunol 33(2):465–473

    PubMed  Google Scholar 

  84. 84.

    Kim J, Koh JK, Lee EY et al (2009) Serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and pentraxin 3 (PTX3) as markers of infection in febrile patients with systemic lupus erythematosus. Clin Exp Rheumatol 27(5):773–778

    PubMed  Google Scholar 

  85. 85.

    Reading PC, Bozza S, Gilbertson B et al (2008) Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. J Immunol 180(5):3391–3398

    PubMed  Google Scholar 

  86. 86.

    Sprong T, Peri G, Neeleman C et al (2009) Pentraxin 3 and Creactive protein in severe meningococcal disease. Shock 31(1):28–32

    PubMed  Google Scholar 

  87. 87.

    He X, Han B, Liu M et al (2007) Long pentraxin 3 in pulmonary infection and acute lung injury. Am J Physiol Lung Cell Mol Physiol 292(5):L1039–L1049

    PubMed  Google Scholar 

  88. 88.

    Garlanda C, Hirsch E, Bozza S et al (2002) Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420(6912):182–186

    PubMed  Google Scholar 

  89. 89.

    Mauri T, Bellani G, Patroniti N et al (2010) Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality. Intensive Care Med 36(4):621–629

    PubMed  Google Scholar 

  90. 90.

    Bozza S, Bistoni F, Gaziano R et al (2006) Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation. Blood 108(10):3387–3396

    PubMed  Google Scholar 

  91. 91.

    Soares AC, Souza DG, Pinho V et al (2006) Dual function of the long pentraxin PTX3 in resistance against pulmonary infection with Klebsiella pneumoniae in transgenic mice. Microbes Infect 8(5):1321–1329

    PubMed  Google Scholar 

  92. 92.

    Inforzato A, Peri G, Doni A et al (2006) Structure and function of the long pentraxin PTX3 glycosidic moiety: fine-tuning of the interaction with C1q and complement activation. Biochemistry 45(38):11540–11551

    PubMed  Google Scholar 

  93. 93.

    Franz S, Gaipl US, Munoz LE et al (2006) Apoptosis and autoimmunity: when apoptotic cells break their silence. Curr Rheumatol Rep 8(4):245–247

    PubMed  Google Scholar 

  94. 94.

    Camozzi M, Zacchigna S, Rusnati M et al (2005) Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo. Arterioscler Thromb Vasc Biol 25:1837–1842

    PubMed  Google Scholar 

  95. 95.

    Zanetti M, Bosutti A, Ferreira C et al (2009) Circulating pentraxin 3 levels are higher in metabolic syndrome with subclinical atherosclerosis: evidence for association with atherogenic lipid profile. Clin Exp Med 9(3):243–248

    PubMed  Google Scholar 

  96. 96.

    Augusto JF, Onno C, Blanchard S et al (2009) Detection of anti-PTX3 autoantibodies in systemic lupus erythematosus. Rheumatology (Oxford) 48(4):442–444

    Google Scholar 

  97. 97.

    Bassi N, Ghirardello A, Blank M et al (2010) IgG anti-pentraxin3 antibodies in systemic lupus erythematosus. Ann Rheum Dis 69(9):1704–1710

    PubMed  Google Scholar 

  98. 98.

    Sherer Y, Gorstein A, Fritzler MJ et al (2004) Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients. Semin Arthritis Rheum 34:501–537

    PubMed  Google Scholar 

  99. 99.

    Sjowall C, Wettero J (2007) Pathogenic implications for autoantibodies against C-reactive protein and other acute phase proteins. Clin Chim Acta 378:13–23

    PubMed  Google Scholar 

  100. 100.

    Rovere P, Peri G, Fazzini F et al (2000) The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen presenting dendritic cells. Blood 96:4300–4306

    PubMed  Google Scholar 

  101. 101.

    Bussolati B, Peri G, Salvidio G et al (2003) The long pentraxin PTX3 is synthesized in IgA glomerulonephritis and activates mesangial cells. J Immunol 170:1466–1472

    PubMed  Google Scholar 

  102. 102.

    Lalvani A, Meroni PL, Millington KA et al (2008) Recent advances in diagnostic technology: applications in autoimmune and infectious diseases. Clin Exp Rheumatol 26(1 Suppl 48):S62–S66

    PubMed  Google Scholar 

  103. 103.

    Doria A, Briani C (2008) Primary prevention of systemic lupus erythematosus. Nat Clin Pract Rheumatol 4(11):576–577

    PubMed  Google Scholar 

  104. 104.

    Doria A, Arienti S, Rampudda M et al (2008) Preventive strategies in systemic lupus erythematosus. Autoimmun Rev 7:192–197

    PubMed  Google Scholar 

  105. 105.

    Doria A, Briani C (2008) Lupus: improving long-term prognosis. Lupus 17:166–170

    PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy

    Margherita Zen, Nicola Bassi, Carla Campana, Silvano Bettio, Elena Tarricone, Linda Nalotto & Anna Ghirardello

  2. Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy

    Andrea Doria

Authors
  1. Margherita Zen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicola Bassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carla Campana
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Silvano Bettio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elena Tarricone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Linda Nalotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anna Ghirardello
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrea Doria
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Doria.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zen, M., Bassi, N., Campana, C. et al. Protective molecules and their cognate antibodies: new players in autoimmunity. Autoimmun Highlights 1, 63–72 (2010). https://doi.org/10.1007/s13317-010-0010-8

Download citation

Keywords

  • Autoimmunity
  • Apoptosis
  • Complement
  • Pentraxins
  • Autoantibodies

Autoimmunity Highlights

ISSN: 2038-3274

Contact us