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Background: Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown.Case Presentation: A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation.Conclusions: We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH. [ABSTRACT FROM AUTHOR]

Vesicles released by cells have been described using various names, including exosomes, microparticles, microvesicles and ectosomes. Here we propose to differentiate clearly between ectosomes and exosomes according to their formation and release. Whereas exosomes are formed in multi-vesicular bodies, ectosomes are vesicles budding directly from the cell surface. Depending upon the proteins expressed, exosomes activate or inhibit the immune system. One of the major properties of exosomes released by antigen-presenting cells is to induce antigen-specific T cell activation. Thus, they have been used for tumour immunotherapy. By contrast, the major characteristics of ectosomes released by various cells, including tumour cells, polymorphonuclear leucocytes and erythrocytes, are the expression of phosphatidylserine and to have anti-inflammatory/immunosuppressive activities similarly to apoptotic cells. [ABSTRACT FROM AUTHOR]

Autoantibodies against C1q have been described in many immune-complex diseases including hypocomplementaemic urticarial vasculitis and systemic lupus erythematosus (SLE). No study has focused on the role of anti-C1q antibodies in hepatitis C virus (HCV) infection. The aim of this study was (i) to evaluate the prevalence of anti-C1q antibodies in HCV infection; and (ii) to analyse the association of anti-C1q antibodies with clinical and biological features of HCV–mixed cryoglobulinaemia (MC) vasculitis. We searched for anti-C1q antibodies using an enzyme-linked immunosorbent assay (ELISA) test in 111 HCV patients (75 had cryoglobulin and 23 systemic vasculitis), 60 SLE patients and 109 blood donors. Anti-C1q antibodies were detected in 26% of HCV patients compared to 10% of healthy donors ( P < 0·01), and 38% in patients with SLE. Although there was a higher prevalence of anti-C1q antibodies among HCV patients with type III cryoglobulin (50%, P < 0·01), the overall prevalence of anti-C1q antibodies was similar in HCV patients being cryoglobulin-positive or cryoglobulin-negative (26% versus 25%, P = 0·98). A significant association was found between anti-C1q antibodies and low C4 fraction of complement ( P < 0·05). No association was found between anti-C1q antibodies and HCV genotype, severity of liver disease or with specific clinical signs of HCV–MC vasculitis. This study shows an increased prevalence of anti-C1q antibodies in HCV-infected patients. Anti-C1q antibodies were associated with low C4 levels. No association was found between anti-C1q antibodies and HCV–MC vasculitis, nor between anti-C1q antibodies and cryoglobulinaemia. [ABSTRACT FROM AUTHOR]

SUMMARY The acquired loss of CR1 (CD35) on erythrocytes in specific autoimmune diseases and chronic infections may be due to autoAb against CR1. An ELISA using rCR1 was established to measure antiCR1 IgG autoAb. Plasma containing alloAb to polymorphism on CR1 (Knops blood group Ab) reacted strongly against rCR1 and were used as positive controls. AntiCR1 Ab was found in 3/90 (3·5%) plasma samples from healthy blood donors. The binding of these Ab was not inhibited by high salt concentrations. AntiCR1 Ab were present in the IgG fractions of plasma, and they bound to rCR1 on Western Blot. Affinity chromatography on rCR1-sepharose depleted the plasma of antiCR1, and the acid-eluted fractions contained the antiCR1 Ab. An increased frequency of antiCR1 autoAb was found in patients with SLE (36/78; 46%), liver cirrhosis (15/41; 36%), HIV infection (23/76; 30%) (all P < 0·0001), and in patients with anticardiolipin Ab (4/21; 19%, P < 0·01) multiple sclerosis (7/50; 14%, P < 0·02), and myeloma (autoAb (8/56; 14%, P < 0·02), but not in those with acute poststreptococcal glomerulonephritis (1:32; 3%). Because C1q binds to CR1, antiC1q Ab were analysed in the same patients. There was no correlation between levels of antiC1q and antiCR1 autoAb. In HIV patients, levels of antiCR1 did not correlate with low CR1 levels expressed on erythrocytes or soluble CR1 in plasma. The binding of antiCR1 autoAb to rCR1 fixed on ELISA plates was not inhibited by soluble rCR1 or by human erythrocyte CR1, in contrast to alloAb and one SLE serum, which induced partial blockade. Thus, antiCR1 autoAb recognize mostly CR1 epitope(s) not present on the native molecule, suggesting that they are not directly involved in the loss of CR1. Rather antiCR1 autoAb might indicate a specific immune response to denatured CR1. [ABSTRACT FROM AUTHOR]

Objectives – To evaluate the treatment effect of recombinant interferon‐α2a (rIFN‐α2a) on complement activation and regulation in MS patients. Material and methods – Plasma levels of the complement activation products C3bc and terminal complement complex (TCC) and serum levels of the complement regulatory proteins, complement receptor 1, CR1 (CD35) and the membrane inhibitor of reactive lysis, protectin (CD59), were determined by enzyme‐linked immunosorbent assay (ELISA) in MS patients treated with IFN‐α2a (14 patients) or placebo (7 patients). Results – The level of soluble CD35 decreased while the level of TCC and to a lesser degree C3bc increased in the IFN‐α2a treated patients during the initial part of the treatment. There was also a concomitant reduction of leukocytes in the same patients. Conclusions – The results indicate that complement is activated during the initial phase of rIFN‐α2a treatment. This could partly be due to a concomitant reduction in soluble CD35. [ABSTRACT FROM AUTHOR]

Autoantibodies against the first component of the classical pathway of complement (anti-C1q) can be found in a number of autoimmune and renal diseases. They are best described in patients with Systemic Lupus Erythematosus (SLE). In adult patients with SLE, there is a strong correlation between the occurrence of anti-C1q and severe lupus nephritis. However, the role of anti-C1q in children with SLE has not yet been determined. Furthermore, the clinical importance of anti-C1q in other forms of glomerulonephritis (GN) remains to be elucidated. The aim of this study was to investigate the role of anti-C1q in children with different forms of GN including SLE nephritis. 100 children with different forms of GN were analyzed (52m, 48 f, age range 2 to17, median12 years) and compared to 29 healthy controls (age range 5 to 17, median 12 years). Renal biopsies were available in 62 patients. From the patients 35 had acute and 65 chronic GN. In the group with acute GN 14 had post-streptococcal GN (APGN) and 21 other causes. In the group with chronic GN 11 patients had proliferative lupus nephritis (WHO class III or IV). In acute GN only patients with APGN were positive for anti-C1q (3/14). From the APGN patients only the 3 anti-C1q positive did not resolve spontaneously. In chronic GN, anti-C1q were mainly found in patients with lupus nephritis (6/11). From the 6 anti-C1q positive SLE patients 5 had clinically active and one had inactive GN. Of the anti- C1q negative SLE patients, two had active lupus nephritis. One of them was under aggressive long-term immunosupression, the other one had spontaneously improving disease in spite of a positive renal biopsy. Another 6 patients with chronic GN were anti-C1q positive: 5 with mesangioproliferative GN (5/26) and 1 with Rheumatoid vasculitis. In conclusion, as observed in adults, anti-C1q are associated with active lupus nephritis. In children with APGN anti-C1q were only found in patients without spontaneous resolution of the disease suggesting a disease modifying role of anti-C1q in APGN. [ABSTRACT FROM AUTHOR]