The main objective of this study is to determine the relationship between the activity of DNase1 and the clinical and immunological features in patients with systemic lupus erythematosus (SLE). A total of 66 patients (8 men and 58 women) diagnosed with SLE according to the American College of Rheumatology (ACR) SLE classification criteria were included in the study. Sixty-two sera from healthy blood donors were also included as controls. Epidemiological, clinical, immunological and therapeutical features for each patient were obtained. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). DNase1 activity was determined by using a radial enzyme diffusion method. Statistical analysis was performed using SPSS 12.0 software, with significant P value <0.05. Dnase1 activity was lower in patients with SLE than in the control group: 13.69 ± 8.52 μg/mL vs 24.75 ± 12.32 μg/mL, respectively (P < 0.005). No statistical relationship was found between DNase1 activity and disease evolution time, hypertension, presence of absolute or relative proteinuria, SLEDAI, new clinical manifestations, anti-Ro antibodies, anti-La antibodies, anti-RNP antibodies, anti-DNA antibodies, anti-cardiolipin antibodies, lupus anticoagulant, or with the treatment pattern received by the patients. Although important differences in DNase1 activity were found between patients with or without anti-Sm antibodies, they did not reach statistical significance. DNase1 activity was significantly lower in patients with SLE. Nevertheless, we did not find further relationships with any other of the epidemiological, clinical, immunological or therapeutical variables considered.
1 Sherer Y Gorstein A Fritzler MJ Shoenfeld Y . Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients. Semin Arthritis Rheum2004; 34: 501–537.
2.
2 Rahman A Kumar S Potter KN . Anti-DNA antibodies–structure and function. Lupus2002; 11: 776–779.
3.
3 Blatt NB Glick GD . Anti-DNA autoantibodies and systemic lupus erythematosus. Pharmacol Ther1999; 83: 125–139.
5 White S Rosen A . Apoptosis in systemic lupus erythematosus. Curr Opin Rheumatol2003; 15: 557–562.
6.
6 Dieker JW van der Vlag J Berden JH . Triggers for anti-chromatin autoantibody production in SLE. Lupus2002; 11: 856–864.
7.
7 Nagata S . Mutations in the Fas antigen gene in lpr mice. Semin Immunol1994; 6: 3–8.
8.
8 Watanabe-Fukunaga R Brannan CI Copeland NG Jenkins NA Nagata S . Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature1992; 356: 314–317.
9.
9 Roths JB Murphy ED Eicher EM . A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice. J Exp Med1984; 159: 1–20.
10.
10 Herrmann M Winkler T Gaipl U Lorenz H Geiler T Kalden JR . Etiopathogenesis of systemic lupus erythematosus. Int Arch Allergy Immunol2000; 123: 28–35.
11.
11 Herrmann M Voll RE Zoller OM Hagenhofer M Ponner BB Kalden JR . Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum1998; 41: 1241–1250.
12.
12 Kalden JR . Defective phagocytosis of apoptotic cells: possible explanation for the induction of autoantibodies in SLE. Lupus1997; 6: 326–327.
13.
13 Tax WJ Kramers C van Bruggen MC Berden JH . Apoptosis, nucleosomes, and nephritis in systemic lupus erythematosus. Kidney Int1995; 48: 666–673.
14.
14 Walport MJ . Lupus, DNase and defective disposal of cellular debris. Nat Genet2000; 25: 135–136.
15.
15 Graham KL Utz PJ . Sources of autoantigens in systemic lupus erythematosus. Curr Opin Rheumatol2005; 17: 513–517.
17 Banchereau J Steinman RM . Dendritic cells and the control of immunity. Nature1998; 392: 245–252.
18.
18 Albert ML Sauter B Bhardwaj N . Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature1998; 392: 86–89.
19.
19 Savill J Dransfield I Gregory C Haslett C . A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol2002; 2: 965–975.
20.
20 Henson PM Bratton DL Fadok VA . The phosphatidylserine receptor: a crucial molecular switch. Nat Rev Mol Cell Biol2001; 2: 627–633.
21.
21 Rosen A Casciola-Rosen L . Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ1999; 6: 6–12.
22.
22 Cragg MS Howatt WJ Bloodworth L Anderson VA Morgan BP Glennie MJ . Complement mediated cell death is associated with DNA fragmentation. Cell Death Differ2000; 7: 48–58.
23.
23 Mannherz HG Peitsch MC Zanotti S Paddenberg R Polzar B . A new function for an old enzyme: the role of DNase I in apoptosis. Curr Top Microbiol Immunol1995; 198: 161–174.
24.
24 Napirei M Wulf S Mannherz HG . Chromatin breakdown during necrosis by serum Dnase1 and the plasminogen system. Arthritis Rheum2004; 50: 1873–1883.
25.
25 Laskowski M . Deoxyribonuclease I.3rd ed.NY: New York Academic Press; 1971.
26.
26 Lacks SA . Deoxyribonuclease I in mammalian tissues. Specificity of inhibition by actin. J Biol Chem1981; 256: 2644–2648.
27.
27 Chitrabamrung S Rubin RL Tan EM . Serum deoxyribonuclease I and clinical activity in systemic lupus erythematosus. Rheumatol Int1981; 1: 55–60.
28.
28 Napirei M Karsunky H Zevnik B Stephan H Mannherz HG Moroy T . Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet2000; 25: 177–181.
29.
29 Macanovic M Lachmann PJ . Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion assay. Clin Exp Immunol1997; 108: 220–226.
30.
30 Boes M Schmidt T Linkemann K Beaudette BC Marshak-Rothstein A Chen J . Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc Natl Acad Sci U S A2000; 97: 1184–1189.
31.
31 Ehrenstein MR Cook HT Neuberger MS . Deficiency in serum immunoglobulin (Ig)M predisposes to development of IgG autoantibodies. J Exp Med2000; 191: 1253–1258.
32.
32 Korb LC Ahearn JM . C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J Immunol1997; 158: 4525–4528.
33.
33 Gaipl US Kuenkele S Voll RE . Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death. Cell Death Differ2001; 8: 327–334.
34.
34 Fishelson Z Attali G Mevorach D . Complement and apoptosis. Mol Immunol2001; 38: 207–219.
35.
35 Bickerstaff MC Botto M Hutchinson WL . Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med1999; 5: 694–697.
36.
36 Butler PJ Tennent GA Pepys MB . Pentraxin-chromatin interactions: serum amyloid P component specifically displaces H1-type histones and solubilizes native long chromatin. J Exp Med1990; 172: 13–18.
37.
37 Teh LS Bedwell AE Isenberg DA . Antibodies to protein P in systemic lupus erythematosus. Ann Rheum Dis1992; 51: 489–494.
38.
38 Chitrabamrung S Bannett JS Rubin RL Tan EM . A radial diffusion assay for plasma and serum deoxyribonuclease I. Rheumatol Int1981; 1: 49–53.
39.
39 Licht R Dieker JW Jacobs CW Tax WJ Berden JH . Decreased phagocytosis of apoptotic cells in diseased SLE mice. J Autoimmun2004; 22: 139–145.
40.
40 Bell DA Morrison B VandenBygaart P . Immunogenic DNA-related factors. Nucleosomes spontaneously released from normal murine lymphoid cells stimulate proliferation and immunoglobulin synthesis of normal mouse lymphocytes. J Clin Invest1990; 85: 1487–1496.
41.
41 Gaipl US Sheriff A Franz S . Inefficient clearance of dying cells and autoreactivity. Curr Top Microbiol Immunol2006; 305: 161–176.
42.
42 Denny MF Chandaroy P Killen PD . Accelerated macrophage apoptosis induces autoantibody formation and organ damage in systemic lupus erythematosus. J Immunol2006; 176: 2095–2104.
43.
43 Gaipl US Beyer TD Heyder P . Cooperation between C1q and DNase I in the clearance of necrotic cell-derived chromatin. Arthritis Rheum2004; 50: 640–649.
44.
44 Pisetsky DS Jiang N . The generation of extracellular DNA in SLE: the role of death and sex. Scand J Immunol2006; 64: 200–204.
45.
45 Lockshin MD . Sex ratio and rheumatic disease: excerpts from an Institute of Medicine report. Lupus2002; 11: 662–666.
46.
46 Lockshin MD . Invited review: sex ratio and rheumatic disease. J Appl Physiol2001; 91: 2366–2373.
47.
47 Lazarides E Lindberg U . Actin is the naturally occurring inhibitor of deoxyribonuclease I. Proc Natl Acad Sci U S A1974; 71: 4742–4746.
48.
48 Macanovic M Sinicropi D Shak S Baughman S Thiru S Lachmann PJ . The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone. Clin Exp Immunol1996; 106: 243–252.
49.
49 Yasutomo K Horiuchi T Kagami S . Mutation of DNASE1 in people with systemic lupus erythematosus. Nat Genet2001; 28: 313–314.
50.
50 Tew MB Johnson RW Reveille JD Tan FK . A molecular analysis of the low serum deoxyribonuclease activity in lupus patients. Arthritis Rheum2001; 44: 2446–2447.
51.
51 Balada E Ordi-Ros J Hernanz S . DNASE I mutation and systemic lupus erythematosus in a Spanish population: comment on the article by Tew, et al.. Arthritis Rheum2002; 46: 1974–1976 author reply 1976–1977.
52.
52 Nadano D Yasuda T Kishi K . Measurement of deoxyribonuclease I activity in human tissues and body fluids by a single radial enzyme-diffusion method. Clin Chem1993; 39: 448–452.
53.
53 Sallai K Nagy E Derfalvy B Muzes G Gergely P . Antinucleosome antibodies and decreased deoxyribonuclease activity in sera of patients with systemic lupus erythematosus. Clin Diagn Lab Immunol2005; 12: 56–59.
