Functional complement C1q abnormality leads to impaired immune complexes and apoptotic cell clearance.

C1q plays a key role in apoptotic cell and immune complex removal. Its absence contributes to the loss of tolerance toward self structures and development of autoimmunity. C1q deficiencies are extremely rare and are associated with complete lack of C1q or with secretion of surrogate C1q fragments.

Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy that associates, in 70% of cases, with genetic or acquired disorders leading to dysregulation of the alternative pathway of complement. Autoantibody directed against Factor H causes at least 6% to 10% of aHUS cases, but only a few clinical reports are available. Here, we describe the clinical, biologic, genetic features, treatment, and outcome of 45 patients who presented with aHUS associated with anti-FH autoantibody.

Atypical hemolytic uremic syndrome and mutation analysis of factor H gene in two Tunisian families.

We carried out a protein and genetic investigation of the factor H gene mutations within two families presenting with a diagnostic suspicion of atypical hemolytic uremic syndrome (aHUS). The results within the patients of the first family revealed a factor H-deficiency. Direct sequencing allowed the detection of a 4-nucleotide deletion in the factor H gene.

Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome.

Genetic studies have shown that mutations of complement inhibitors such as membrane cofactor protein, Factors H, I, or B and C3 predispose patients to atypical hemolytic uremic syndrome (aHUS). Factor I is a circulating serine protease that inhibits complement by degrading C3b and up to now only a few mutations in the CFI gene have been characterized. In a large cohort of 202 patients with aHUS, we identified 23 patients carrying exonic mutations in CFI.

Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome.

Complement is a major innate immune defense against pathogens, tightly regulated to prevent host tissue damage. Atypical hemolytic uremic syndrome (aHUS) is characterized by endothelial damage leading to renal failure and is highly associated with abnormal alternative pathway regulation. We characterized the functional consequences of 2 aHUS-associated mutations (D(254)G and K(325)N) in factor B, a key participant in the alternative C3 convertase.

Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS.

Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome.

The HELLP syndrome, defined by the existence of hemolysis, elevated liver enzymes, and low platelet count, is a serious complication of pregnancy-related hypertensive disorders and shares several clinical and biologic features with thrombotic microangiopathy (TMA). Several recent studies have clearly shown that an abnormal control of the complement alternative pathway is a major risk for the occurrence of a peculiar type of TMA involving mainly the kidney. The aim of this study was to screen for complement abnormalities in 11 patients with HELLP syndrome and renal involvement.

Hereditary complement deficiency and lupus: report of four Tunisian cases.

The aim of the study was to assess the clinical and immunological profile of lupus erythematosus (LE) patients with inherited complement deficiency (ICD). A laboratory-based study was conducted in which all LE patients with hypocomplementemia were included. ICD was assessed by hemolytic and antigenic assays.

Pediatric systemic lupus erythematosus with C1q deficiency.

Hereditary deficiency of each component of the classical pathway is associated with increased susceptibility to lupus erythematosus (LE). Both the severity of the disease and the strength of this association are greatest for homozygous C1q deficiency, which is extremely rare. In fact, more than 90% of all individuals with deficiency of this component have LE.

Hereditary complement C7 deficiency in nine families: subtotal C7 deficiency revisited.

Deficiencies in terminal complement components, including the component C7, are uncommon and associated with an increased risk of recurrent systemic neisserial infection. A total of 22 molecular defects have been reported in the C7 gene with both complete (C7Q0) and subtotal (C7SD) C7 deficiencies. In this study we report the molecular basis of nine new cases of C7 deficiencies that were characterized by exon-specific sequence analysis.

Unusual clinical severity of complement membrane cofactor protein-associated hemolytic-uremic syndrome and uniparental isodisomy.

Atypical hemolytic-uremic syndrome (aHUS; OMIM 235400) is genetically and clinically heterogeneous. Mutations in membrane cofactor protein (MCP; CD46), a widely expressed complement regulator, predispose to recurrent forms of the disease. Patients carrying MCP mutations have a favorable clinical outcome in comparison to those with factor H (CFH) or factor I (IF) mutations, which lead in most cases to end-stage renal failure.

Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome.

Introduction: Abnormal control of the complement alternative pathway (CAP) (factor H, factor I and membrane cofactor protein (MCP) deficiencies) is a well established risk factor for the occurrence of haemolytic uraemic syndrome (HUS). In some instances, HUS may be associated with an unusual glomerulonephritis with isolated C3 deposits (glomerulonephritis C3). We determined whether HUS and glomerulonephritis C3 share common genetic susceptibility factors.

Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. The non-Shiga toxin-associated HUS (atypical HUS [aHUS]) has been shown to be a disease of complement dysregulation. Mutations in the plasma complement regulators factor H and factor I and the widely expressed membrane cofactor protein (MCP; CD46) have been described recently.

Anti-Factor H autoantibodies associated with atypical hemolytic uremic syndrome.

Several studies have demonstrated genetic predisposition in non-shigatoxin-associated hemolytic uremic syndrome (HUS), involving regulatory proteins of the complement alternative pathway: Factor H (FH) and membrane co-factor protein (CD46). Regarding the observations of thrombotic thrombocytopenic purpura patients, in whom a von Willebrand factor protease (ADAMST-13) deficiency may be inherited or acquired secondary to IgG antibodies, it was speculated that HUS might occur in a context of an autoimmune disease with the development of anti-FH antibodies leading to an acquired FH deficiency. The presence of FH autoantibodies was investigated by an ELISA method using coated purified human FH in a series of 48 children who presented with atypical HUS and were recruited from French university hospitals.

[Investigation of the complement system in clinical practice].

The complement system plays an important role in defence of the host against infection and in the clearance of immune complexes. Defects in complement proteins are often associated with infections or auto/immune complex diseases. Investigation of complement is useful for diagnosis and following of auto-immune diseases.

Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases.

Factor H (FH) is the major regulatory protein of the complement alternative pathway, with a structure consisting of a tandem array of 20 homologous units, called short consensus repeats (SCR). Reported are 16 FH-deficient patients. Among six patients with homozygous deficiency, four presented with membranoproliferative glomerulonephritis, and two with atypical hemolytic uremic syndrome (HUS).

Prevalence of monoclonal gammopathy in patients presenting with acquired angioedema type 2.

Purpose: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in patients with lymphoproliferative disorders, whereas acquired angioedema type 2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to be associated with lymphoproliferative disease. We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2.

Subjects And Methods: Plasma concentrations and functional activity of complement components were measured by conventional techniques.