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Objective. To evaluate the specificity of expression patterns of cell-free circulating microRNAs (miRNAs) in systemic lupus erythematosus (SLE).Methods. Total RNA was purified from plasma, and 45 different specific, mature miRNAs were determined using quantitative reverse transcriptionpolymerase chain reaction assays. A total of 409 plasma samples were obtained from 364 different patients with SLE, healthy control subjects, and control subjects with other autoimmune diseases. The results in the primary cohort of 62 patients with SLE and 29 healthy control subjects were validated in 2 independent cohorts: a validation cohort comprising 68 patients with SLE and 68 healthy control subjects, and a disease control cohort comprising 20 patients with SLE (19 of whom were from the other validation cohort), 46 healthy control subjects, 38 patients with vasculitis, 18 patients with rheumatoid arthritis, and 20 immunosuppressed patients.Results. Seven miRNAs were statistically significantly differentially expressed in plasma from patients with SLE. The expression of miRNA-142-3p (miR-142-3p) and miR-181a was increased, and the expression of miR-106a, miR-17, miR-20a, miR-203, and miR-92a was decreased. In addition, the expression of miR-342-3p, miR-223, and miR-20a was significantly decreased in SLE patients with active nephritis. A predictive model for SLE based on 2 or 4 miRNAs differentiated patients with SLE from control subjects (76% accuracy) when validated independently (P < 2 ؋ 10 ؊9 ). Use of the 4-miRNA model provided highly significant differentiation between the SLE group and disease controls, except for those with vasculitis.Conclusion. Circulating miRNAs are systematically altered in SLE. A 4-miRNA signature was diagnostic of SLE, and a specific subset of miRNA profiles was associated with nephritis. All of the signature miRNAs target genes in the transforming growth factor ␤ signaling pathways. Other targets include regulation of apoptosis, cytokine-cytokine receptors, T cell development, and cytoskeletal organization. These findings highlight possible dysregulated pathways in SLE and suggest that circulating miRNA patterns distinguish SLE from other immunoinflammatory phenotypes.The autoimmune disease systemic lupus erythematosus (SLE) is characterized by multiple immunologic abnormalities including the presence of circulating antinuclear antibodies and a sustained type I interferon (IFN) response (1), with up-regulation of type I IFN-

Anti-GBM disease is now a preferred term for what was earlier called Goodpasture's syndrome or Goodpasture's disease  Anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation  The diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease  Therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases  20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease.

Proteinase 3 (PR3) is found in granules of all neutrophils but also on the plasma membrane of a subset of neutrophils (mPR3). CD177, another neutrophil protein, also displays a bimodal surface expression. In this study, we have investigated the coexpression of these two molecules, as well as the effect of cell activation on their surface expression. We can show that CD177 is expressed on the same subset of neutrophils as mPR3. Experiments show that the expression of mPR3 and CD177 on the plasma membrane is increased or decreased in parallel during cell stimulation or spontaneous apoptosis. Furthermore, we observed a rapid internalization and recirculation of mPR3 and plasma membrane CD177, where all mPR3 is replaced within 30 min. Our findings suggest that the PR3 found on the plasma membrane has its origin in the same intracellular storage as CD177, i.e., secondary granules and secretory vesicles and not primary granules. PR3- and CD177-expressing neutrophils constitute a subpopulation of neutrophils with an unknown role in the innate immune system, which may play an important role in diseases such as Wegener's granulomatosis and polycythemia vera.

SUMMARYInteractions between plasma proteins and MPO were studied. The protein fraction of normal plasma and serum was shown to exhibit an inhibitory effect on the peroxidase activity of MPO. Most of the inhibitory effect could be retained on an MPO-coupled affinity chromatography column. In particular, a protein with apparent mol. wt of 130 kD showed affinity for MPO. The protein was identified as ceruloplasmin by N-terminal amino acid sequencing and immunochemistry. During separation procedures the peroxidase inhibitory effect was limited to ceruloplasmin-containing fractions of plasma. Purified ceruloplasmin inhibited the peroxidase activity of MPO in a concentration-dependent manner, and exhibited selective binding to MPO-coated microtitre plates. This binding could be inhibited by MPO dissolved in buffer. Correspondingly the binding of MPO to ceruloplasmin-coated plates could be blocked by ceruloplasmin in solution, showing a physical interaction to occur between the two proteins under physiological conditions. We also found affinity to exist between MPO and C3 (and its C3d-containing fragments). However, C3 and C3 fragments did not inhibit the peroxidase reaction in vitro. We propose that ceruloplasmin takes part in the clearance and inactivation of MPO, in vivo. We also speculate that impaired inactivation of MPO may have a pathophysiological role in inflammatory diseases characterized by autoantibodies to MPO, such as rapidly progressive glomerulonephritis with P-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies).