DNASE I mutation and systemic lupus erythematosus in a Spanish population: Comment on the article by Tew et al

Abstract

High-resolution ultrasound for the study of target joints in rheumatoid arthritis To the Editor: Conventional radiography remains the "gold standard" for the evaluation of joint damage and its progression in rheumatoid arthritis (RA), but changes may not be evident radiographically until late in the disease course (1). Magnetic resonance imaging (MRI) has been used to study patients with early RA, but high cost and lack of standardization limit its use (2). Several studies have now shown that high-resolution ultrasound (US) of the metacarpophalangeal (MCP) joints can be very informative in the evaluation of RA of various durations (3-5). Erosions have been visualized in selected hand joints (second MCP) and foot joints (fifth metatarsophalageal [MTP]) (5). In fact, detection of more erosions per joint and per patient with US as compared with radiography was demonstrated by Wakefield et al in a recent study reported in Arthritis & Rheumatism (3). The present pilot study was undertaken to assess the feasibility of performing US in selected (target) joints of patients with RA, and to determine if this technique offers additional information beyond that obtained with conventional radiography. MRI was chosen as a comparator method because of its high sensitivity. Our Institutional Review Board approved this study. Ten unselected patients with RA according to the criteria of the American College of Rheumatology (formerly, the American Rheumatism Association) (6) and 5 healthy volunteers who, as a group, were of comparable age (mean 45 years), sex (80% women), and ethnicity (80% white) with the patients were studied. The duration of RA was Ͻ2 years in 2 patients, 3-5 years in 5, and Ͼ5 years in 3. Six of the 10 patients were positive for IgM rheumatoid factor. Five of the 10 were receiving a disease-modifying antirheumatic drug (methotrexate in 4 of the 5); 3 other patients were receiving anti-tumor necrosis factor therapy. Joints selected for US imaging included the second and fifth MCP joints and the fifth MTP joints. These joints were selected on the basis of their likelihood of early involvement in RA as well as their easy accessibility with the US probe. The first MTP joints, not considered targets for involvement early in the course of RA, were also examined because of their easy accessibility with the US probe. Conventional radiographs of the hands/wrists and feet were obtained. These included 3 views (anteroposterior, lateral, and oblique) obtained using standard techniques (Kilovolt peak 54, milliampere-second 2.5, fine detail film-screen combination). Coronal T1-weighted MR images of the hands and feet were obtained using a 1.5T body scanner (Signa; GE, Milwaukee, WI), dedicated extremity coils, and the following parameters: repetition time 500 msec, echo time 15 msec, 256 ϫ 192 matrix, 3 mm thickness with 0.5 mm gap, field of view 20 cm). Finally, US of the joints as noted above was performed by one of us (RL-B), using 10-15 MHz highresolution linear array transducers with small footprints. Indi-2. Molenaar T...

Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus

“…A mutation in the second exon of the DNASE1 gene has been reported (29), but its low prevalence does not explain the decreased activity of the enzyme in most SLE patients (3,10,21,26).…”

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

“…High titers of IgG against nucleosomal antigens were also found in 2 patients with a heterozygous nonsense mutation in exon 2 of DNase I (42). However, it is obvious that additional genes are involved in the DNA clearance process (43,44).…”

The uptake and degradation of DNA is impaired in macrophages and dendritic cells from NZB/W F1 mice

“…Moreover, DNase I-deficient mice produced by gene targeting show the classical symptoms of SLE, which are the presence of anti-nuclear antibodies and glomerulonephritis [38]. Mutation of DNase I gene has also been found in some SLE patients [39], although not all SLE patients have defects in DNase genes [40][41][42]. Therefore, multiple factors are probably involved in causing the reduced DNase activity in SLE.…”