Complement alternative pathway plays an important, but not clearly understood, role in neutrophil-mediated diseases. We here show that neutrophils themselves activate complement when stimulated by cytokines or coagulation-derived factors. In whole blood, tumor necrosis factor/ formyl-methionyl-leucyl-phenylalanine or phorbol myristate acetate resulted in C3 fragments binding on neutrophils and monocytes, but not on T cells. Neutrophils, stimulated by tumor necrosis factor, triggered the alternative pathway on their surface in normal and C2-depleted, but not in factor B-depleted serum and on incubation with purified C3, factors B and D. This occurred independently of neutrophil proteases, oxidants, or apoptosis. Neutrophil-secreted properdin was detected on the cell surface and could focus "in situ" the alternative pathway activation. Importantly, complement, in turn, led to further activation of neutrophils, with enhanced CD11b expression and oxidative burst. Complement-induced neutrophil activation involved mostly C5a and possibly C5b-9 complexes, detected on tumor necrosis factor-and serum-acti- IntroductionNeutrophils and the complement alternative pathway (AP) are major effectors of cell-mediated and humoral innate immunity. The analysis of complement knockout mice, in experimental inflammatory diseases, shed new light on the participation of complement AP in neutrophil-mediated diseases, such as rheumatoid arthritis, 1 membranoproliferative glomerulonephritis, 2 ischemia-reperfusion injury, 3 and, more recently, antineutrophil cytoplasmic autoantibody (ANCA)-associated small-vessel vasculitis. 4 In an experimental model of ANCA-associated small-vessel vasculitis, the unexpected observation that factor B-deficient mice were protected from the disease, whereas C4-deficient mice were not, 4 revealed the alternative complement pathway as a new partner of this neutrophilmediated disease. It was thus reasonable to propose that neutrophils could participate in the activation of complement AP.If the activation of neutrophils by complement fragments, such as C3a or C5a, is well known, data on complement triggering by neutrophils are scarce. Neutrophil proteases and oxidants have been reported to activate complement in cell-free systems, 5-7 and supernatants of ANCA-activated neutrophils were shown to release unknown complement activating factors. 4 We investigated the ability of the neutrophil surface to activate complement and deposit active complement fragments on their plasma membrane.Complement activation on blood cells is kept under control by fluid phase regulators (ie, plasma factor H and C4b-binding protein) and by cell membrane regulators (ie, decay accelerating factor DAF [CD55] and membrane cofactor protein MCP [CD46]). These regulators prevent the formation and accelerate the decay of C3bBb and C4b2a alternative and classic C3-convertases and act as cofactors for factor I-mediated C3b and C4b proteolysis. Neutrophils also express CR1 (CD35), which is the only cofactor allowing factor I to fully degrade ...

SummaryBackground and objectives ANCA-associated vasculitis (AAV) is treated with potent immunosuppressive regimens. This study sought to determine risk factors associated with infections during first-intention therapy.Design, setting, participants, & measurements This retrospective study involved two separate cohorts of consecutive cases of AAV seen from 2004 to 2011 at two university hospitals. The following were assessed: vasculitis severity; therapy; and periods with no, moderate (lymphocyte count, 0.3-1.03 10 9 /L), or severe (lymphocyte count # 0.3310 9 /L) lymphopenia and neutropenia (neutrophil count # 1.5310 9 /L).Results One hundred patients had a mean age of 57615 years and a Birmingham vasculitis activity score of 7.763.6. Therapy consisted of pulse methylprednisolone (59%), cyclophosphamide (85%), methotrexate (6%), and plasmapheresis (25%) in addition to oral corticosteroids. During follow-up, 53% of patients experienced infection and 28% were hospitalized for infection (severe infection). Only 18% experienced neutropenia, but 72% and 36% presented moderate and severe lymphopenia for a total duration of ,0.1%, 73%, and 8% of the treatment follow-up, respectively. Lower initial estimated GFR, longer duration of corticosteroid use, and presence of lymphopenia were risk factors of infections. The rate was 2.23 events/person-year in the presence of severe lymphopenia compared with 0.41 and 0.19 during periods with moderate or no lymphopenia (P,0.001). Similarly, the rate of severe infections was 1.00 event/person-year with severe lymphopenia and 0.08 and 0.10 with moderate and no lymphopenia (P,0.001). This association remained independent of other risk factors.Conclusions Lymphopenia is frequent during the treatment of AAV, and its severity is associated with the risk of infectious complications.

Background: The appropriate observation period, rate and risk factors of complications after a percutaneous renal biopsy remain debated. Methods: We retrospectively studied native kidney biopsies performed in our institution between January 2007 and July 2011. Outpatients had either an 8- (67%) or a 24-hour (33%) observation period. Results: 312 biopsies were reviewed (287 patients), 51% of patients were female and the mean age was 54 ± 15 years. Half of these biopsies were performed in outpatients. A total of 15% of patients developed a symptomatic hematoma, 9% received a red blood cell transfusion and 1% required an angio-intervention. Eighty-four percent of the complications manifested within the first 8 h, 86% at 12 h and 94% at 24 h. Outpatients experienced significantly less complications, all manifesting within the first 8 h, 14% required an observation period longer than planned. The risk of symptomatic hematoma increased to 11, 20, 35 and 40% in patients with >200, 140-200, 100-140 and <100 × 10⁹/l platelets, respectively (p = 0.002). It also increased in hemodialysis patients (29% compared to 14%, p = 0.02). We found no association of risk with the number of biopsy passes and only a trend with needle size. Conclusion: Symptomatic hematomas occurred in 15% of kidney biopsies and were strongly associated with platelet count and hemodialysis. Outpatients experienced fewer complications; therefore, we can conclude that same-day discharge in selected patients is safe.