Although antinucleosome antibody titers show a correlation with SLEDAI, the association is probably a consequence of the strong correlation between antinucleosome and anti-dsDNA antibody titers, with the second option being an important component of SLEDAI. DNase activity. Within the SLE group, the presence of renal disease experienced no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. Inside a longitudinal study of six SLE individuals, DNase activity did not adhere to disease activity or autoantibody titers. Our results confirm that serum DNase activity is definitely decreased in individuals with SLE, but UAA crosslinker 1 hydrochloride we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide range of pathological autoantibodies. Those directed against chromatin parts, e.g., double-stranded DNA UAA crosslinker 1 hydrochloride (dsDNA), histones, and the nucleosome, are of paramount pathological importance (6, 8, 20). Recent studies of individuals with SLE suggest the increasing diagnostic importance of antinucleosome antibodies, in addition to antibodies directed against dsDNA (1, 17). These circulating antibodies may form immune complexes with their target antigens, the glomerular deposition of which will lead to the development of renal damage (12, 14). The incidence of immune complex-mediated glomerulonephritis (GN) among SLE individuals varies from 30 to 60%. Several studies have confirmed that autoantibodies are produced through an antigen-driven T-cell-dependent mechanism (13, 23, 27). Relating to this model, the defective clearance of apoptotic cell debris predisposes individuals to SLE through the build up of the chromatin parts arising from the dying cells (5, 28). UAA crosslinker 1 hydrochloride DNase I (pancreatic DNase) and DNase II (spleen acid DNase) cleave nucleosomal DNA, which promotes the disposal of circulating nuclear material. DNase I, a glycoprotein having a molecular mass of 30,400 Da, is definitely a cation-binding secretory endonuclease that digests dsDNA inside a sequence-dependent manner (24). DNase II, a glycoprotein having a molecular mass of 45 kDa, is an endonuclease with an acidic pH optimum and no requirement for bivalent cations. UAA crosslinker 1 hydrochloride It is present in lysosomes, nuclei, and some secretions (16). For a long time it has been suspected that problems in DNase I may play a role in the development of SLE and lupus nephritis (11). Rabbit polyclonal to SEPT4 Studies of SLE-prone or DNase I-deficient mouse strains have confirmed this model (15, UAA crosslinker 1 hydrochloride 19). We set out to test the hypothesis that SLE individuals have decreased serum DNase activity compared to those of healthy controls and individuals with undifferentiated connective cells disease (UTCD), a disorder related to SLE. We also investigated the variations in DNase activities and serum antinucleosome levels between two subgroups of SLE individuals, those with and without renal involvement. Finally, the connection between DNase activity and SLE disease activity was also analyzed. MATERIALS AND METHODS A total of 113 SLE individuals (33 with active GN and 18 with a history of GN) were enrolled in the study, after they offered informed consent. Of these 113 individuals, 105 were females and 8 were males (imply standard deviation [SD] age, 38.3 14.1 years; age range, 13 to 79 years). A total of 185 serum samples were from these individuals. Patients were monitored at three outpatient clinics of Semmelweis Medical University or college, Budapest, Hungary, and all fulfilled the revised criteria for SLE of the American College of Rheumatology (25). The sera from nine individuals with UCTD (18) (7 females and 2 males; mean SD age, 45.8 11.9 years) and from 14 healthy individuals (11 females and 3 males; mean SD age, 43 22.1 years) were used as controls. Venous blood samples were taken without anticoagulation; sera were stored at ?20C for up to 1 month. Long-term storage was performed at ?80C. If more than one serum sample was available, the individuals in the cross-sectional studies were characterized by their imply DNase and antibody levels. Individual data were utilized for longitudinal studies. Antinucleosome and anti-dsDNA antibody levels were measured by an enzyme-linked immunosorbent assay (ELISA; Orgentec GmbH, Mainz, Germany), according to the instructions of the manufacturer. Serum DNase activity was also measured by an ELISA (Orgentec), according to the instructions of the manufacturer. Briefly, DNase enzyme from individuals’ sera was allowed to react with the specific substrate coated onto the plate during incubation at 37C for an.