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FRI0132 Decreased serum dnase 1 activity levels in sle patients with active disease

Background DNASE 1 (deoxyribonuclease 1; EC 3.1.21.1) deficient mice have been shown to develop classical symptoms of Systemic Lupus Erythematosus (SLE) with anti-nuclear antibodies in the circulation. Low serum DNASE 1 activity has been reported in patients with SLE. Objectives The aim of this study was to investigate serum DNASE 1 activity in SLE patients in relation to disease activity. In addition, the relationship between the DNASE 1 activity and renal involvement was analysed. Methods Serum samples from fifty patients with SLE (ACR criteria), 39 females and 11 males, mean age 44, were analysed for DNASE 1 activity by the single radial enzyme-diffusion method (SRED) (Nadano et al., 1993). All sera were analysed on three separate occasions and the mean value (pg/ml) from the three experiments was used. Anti-dsDNA antibodies were detected by indirect IFL. SLE disease activity was assessed according to the Systemic Lupus Activity Measure (SLAM). A SLAM score of 7 or above was considered as high. Thirty (60%) had high disease activity (SLE/active), the other 20 patients (SLAM <7) were classified as SLE/inactive. Twenty-six (52%) of the 50 SLE patients had glomerulonephritis, in all cases confirmed by renal biopsy; the other 24 patients (48%) had no clinical signs of renal involvement. The renal biopsies were classified according to the WHO classification. Six patients had WHO class II, 12 WHO class III/IV and 8 WHO class V. Results Serum DNASE 1 levels were significantly lower in the SLE/active patient group as compared to the SLE/inactive patients (12.4 ± 3.8 vs. 16.1 ± 3.7 pg/ml, mean ± SD, p < 0.005). Among the 20 SLE/inactive patients, a trend towards lower serum DNASE 1 levels was noted in patients with renal involvement (n = 9) (14.8 ± 3.6 pg/ml) as compared to patients without renal involvement (n = 11) (17.1 ± 3.5 pg/ml, p = 0.06). However, in SLE/active patients, there was no significant difference in DNASE 1 levels between patients with and without renal involvement. There was no association between the levels of DNASE 1 activity and anti-dsDNA antibody titres. Twenty-five of the patients received prednisolone treatment. Among these patients, low levels of serum DNASE 1 activity were found to be associated with high dose prednisolone therapy (r = -0.552, p < 0.005). Conclusion This study demonstrated low DNASE 1 levels to be associated with high disease activity in SLE patients and may represent a novel marker of disease activity independently of anti-dsDNA antibodies. Further studies are needed to clarify the role of DNASE 1 in SLE manifestations and disease development.