International Immunology Advance Access originally published online on January 30, 2009
International Immunology 2009 21(3):237-243; doi:10.1093/intimm/dxn142
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Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE: a possible explanation for the lack of efficacy of hrDNase I treatment
1 Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, 37134 Verona, Italy
2 Institute G. Gaslini, Department of Immunology, Genova, Italy
3 Department of Experimental Medicine, Section of Histology, University of Genova, Genova, Italy
4 Department of Clinical and Experimental Medicine, Section of Rheumatology, University of Perugia, Perugia, Italy
5 Department of Clinical and Experimental Medicine, Section of Hematology, University of Verona, Verona, Italy
6 Department of Internal Medicine, Section of Clinical Immunology, University of Pisa, Pisa, Italy
Correspondence to: C. Lunardi; E-mail: claudio.lunardi{at}univr.it
The objectives of the study are to evaluate DNase I serum levels and their correlation with soluble Fas (sFas) and soluble Fas ligand (sFasL) and with cell surface Fas expression in patients with systemic lupus erythematosus (SLE), thus contributing to the dysregulated apoptosis typical of the disease. The methods include the following: Serum DNase I levels in patients and in controls were detected using the dot blot method and quantified by densitometry; sFas and sFasL were quantified using an ELISA system. Cell surface Fas expression was evaluated by FACS analysis. Apoptosis was studied by means of internucleosomal DNA degradation using a commercially available kit. The results are as follows: We found a significant difference in DNase I, sFas and sFasL serum levels between patients and controls. Levels of DNase I <7.79 ng ml–1 are more represented in patients with SLE. Active SLE is strongly associated with high sFas levels and detectable sFasL. DNase I does not correlate with sFas or sFasL, whereas it correlates with T cell surface Fas expression that is higher in patients with active SLE than in healthy controls. Finally, administration of exogenous human recombinant DNase (hrDNase) I to freshly isolated T cells up-regulates cell surface Fas expression and induces increased susceptibility to Fas-mediated apoptosis. In conclusion, our findings confirm that DNase I is low in SLE and suggest that it may play a role in apoptosis in SLE by regulating the surface expression of the cell death molecule Fas. This role may contribute to explain the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase I to remove DNA from auto-antigenic nucleoprotein complexes.
Keywords: DNase I, human recombinant DNase I, SLE, soluble Fas/FasL
* These authors contributed equally to this study.
Transmitting editor: L. Moretta
Received 8 September 2008, accepted 8 December 2008.