Background/Purpose: Defective clearance of both nuclesomes and immune complexes has been  suggested to intiate and perpetuate the disease. Defects in DNAse I gene in mice have shown SLE like symptoms, also in humans the decreased levels and levels of DNAse I have been shown. There are few studies in SLE patients looking at these defects, a systemic study is lacking, thus we proposed to study these mechanisms.

Methods: One hundred sixtythree patients ( Female : Male 13:1) were included in the study after written consent were obtained. Eightyfour patients were having active disease as measured by Systemic lupus erythematosus disease activity index (SLEDAI ) core of more than 4. Sera samples were collected and stored in aliquots at -70 degree C till use. DNAse levels in sera  both before and after heating at 56 degree C for 10 minutes to destroy the inhibitors of DNAse such as G protein and actin.  DNAse I level were assayed in the sera of  132 patients and 52 normals individuals were done using Radial Enzyme Diffusion assay and the levels were measured using DNAse I as standard. C3, C4 and CRP were done by nephelometry. Antibodies to  dsDNA and anti-DNAse I antibodies levels were levels in serum were quantitated by ELISA using commercial and in-house ELISA respectively.  The levels of DNAse I , antibodies to DNAse I and CRP were correlated with SLEDAI and between each other statistically.

Results: In patients the median DNAse I levels for pre-heated serum was 2.9 (range 0-39) while the median levels for post heated serum (indicating the inhibitor free levels of DNAse I in serum) was 5.6 (range 3.9-39). In normal individuals the median levels in preheated serum was 8.5 (range 0-26) while median levels for post heated was 13.75 (range 0-39).The DNAse I levels was significantly higher (p<0.0001) in inhbibitor depleted  sera as compared to pre-heated ones in both patients and normals. Further, post heated DNAse I levels, was significantly, (p<0.0001) reduced in patients as compared to normals. However, there was no correlation with activity status of patients as measured by SLEDAI. DNAse I levels significantly correlated with age (r =0.222, p <0.05). CRP, which also helps in clearing nucleosome levels in these patients were not significantly correlated with the levels of C3, C4 and anti-dsDNA antibodies levels. The median antibodies to DNAse I levels was 44.6 arbitrary unit (AU) (range 5.11-1522.08) as compared to healthy controls  of  32.4 AU ( range 7.77-133.08).The level of antibodies to DNAse I was higher in patients compared to normals although difference was not statistically different. Antibodies to DNAse correlated with r=0.18, p=0.26) DNAse I levels. There was no correlation between levels of  anti-DNAse I antibodies with SLEDAI. .

Conclusion: The levels of DNAse I are reduced in the SLE patients and the levels of inhibitor to DNAse I are high in serum of these patients. The levels of anti-DNAse I antibodies are positively correlated with the DNAse I levels. However, there was no correlation of these biomarkers with composite score of disease activity

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-dnase-i-anti-dnase-i-antibodies-crp-and-antibodies-to-crp-relation-to-disease-activity-in-systemic-lupus-eryhtematous-longitudinal-studies/