Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75% ؎ 12.1%) than in the controls (81.3% ؎ 9.25%) (P < 0.001). DNase activity in patients with UCTD (64.9% ؎ 18.2%; P ‫؍‬ 0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3 ؎ 851) than the controls (1.44 ؎ 2.77; P < 0.01) or UCTD patients (39.9 ؎ 57.7; P < 0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but 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 components, e.g., double-stranded DNA (dsDNA), histones, and the nucleosome, are of paramount pathological importance (6,8,20).Recent studies of patients 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 patients varies from 30 to 60%. Several studies have confirmed that autoantibodies are produced through an antigen-driven T-cell-dependent mechanism (13,23,27). According to this model, the defective clearance of apoptotic cell debris predisposes individuals to SLE through the accumulation of the chromatin components arising from the dying cells (5, 28).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 with a molecular mass of 30,400 Da, is a cation-binding secretory endonuclease that digests dsDNA in a sequence-dependent manner (24). DNase II,...

Summary.  Background: We studied 24 Hungarian patients from 23 unrelated families to identify the genetic background of the entire type 3 von Willebrand disease (VWD) population in this country. The current report focuses on the molecular characterization of a novel large deletion. Results: A large partial deletion (delExon1–3) of the 5′‐region of the von Willebrand factor gene (VWF) was detected in 12/48 alleles (25% of all type 3 alleles). The 5′‐deletion breakpoint is located in the untranslated region between VWF and CD9, whereas the 3′ breakpoint is in intron 3 of VWF. Analysis of the breakpoints showed Alu Y and Alu SP repetitive sequences at the ends of the deletion, suggesting that a recombination event caused the subsequent loss of the 35‐kb fragment. DelExon1–3 was not found in any of the other screened populations. Conclusion: We report a large novel deletion including exons 1, 2 and 3 of VWF commonly causing type 3 VWD in the Hungarian population. This mutation, probably caused by an Alu‐mediated recombination event, and subsequently distributed in Hungary by a founder effect, seems to be unique to Hungarian patients with a high allele frequency. Together, delExon1–3 and 2435delC make up 37.5% of the genetic defects in Hungarian patients with VWD type 3. This offers a rational approach to molecular testing of relevant families in Hungary.

In SLE patients, the presence of aPL is a more significant risk factor for the development of thrombosis than the known inherited deficiencies. Based on these data, routine screening for additional hereditary risk factors seems to be unwarranted.

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Receptors specific for the Fc part of IgG (Fc + R) are expressed by several cell types and play diverse roles in immune responses. Impaired function of the activating and inhibitory Fc + R may result in autoimmunity. Thus, the modulation of IgG-Fc + R interaction can be a target for the development of treatments for some autoimmune and inflammatory diseases. This study addresses the localization and functional characterization of linear sequences in human IgG1 which bind to Fc + RII. Peptides with overlapping sequences derived from the CH2 domain of human IgG1 between P 234 and S 298 were synthesized and used in binding and functional experiments. Binding of the peptides to Fc + R was assayed in vitro and ex vivo, and peptides found to interact were functionally tested. The shortest effective peptide was T 256-P 271 complexed by avidin exhibited functional activity; they induced Fc + RIIb-mediated inhibition of the BCR-triggered Ca 2+ response of human Burkitt lymphoma cells, and inflammatory cytokine production (TNF- § and IL-6) by the human monocyte cell line MonoMac. In conclusion, our results suggest that the selected peptides functionally represent the Fc + RII-binding part of IgG1.