BACKGROUND: In vitro levels of complement C3 and C4 proteins are sensitive to storage conditions. To avoid in vitro complement activation when testing is delayed, serum should be frozen at -20degrees C within 2 hr of venipuncture. However, this is impractical in routine laboratory work. Therefore, we investigated alterations in C3 and C4 levels in refrigerated specimens over time and derived formulae to estimate initial levels of complement concentrations in delayed testing. METHODS: Ten fresh specimens were measured for C3 and C4 concentrations and were refrigerated at 4degrees C. We measured C3 and C4 levels in refrigerated samples daily for 4 days using an automated nephelometer (Beckman Coulter Inc., USA). RESULTS: C3 and C4 levels were significantly increased over time in refrigerated specimens (P<0.001, P<0.001, respectively). The increments in C3 and C4 levels were described by the equations: C3 (mg/dL)=3.55x+87.18 (r=0.9909), and C4 (mg/dL)=0.72x+22.3 (r=0.9395), where x=the number of days samples were refrigerated before testing. Increases in C3 and C4 concentrations were described on a percentage basis by the equations: DeltaC3 (%)=4.14x+1.07 (r=0.9903), and DeltaC4 (%)=3.57x+2.48 (r=0.9405). CONCLUSIONS: As the measured C3 and C4 concentrations increased by 3.55 mg/dL (4.1%) and 0.72 mg/dL (3.6%) per day in refrigerated specimens, the levels of C3 and C4 should be adjusted in delayed testing. We proposed that the formulae presented be used to back-calculate initial levels of C3 and C4 concentrations.
Complement Activation ; Complement C3* ; Complement C4 ; Complement System Proteins ; Phlebotomy

The complement system is an innate immune defense machinery comprising components that deploy rapid immune responses and provide efficient protection against foreign invaders and unwanted host elements. The complement system is activated upon recognition of pathogenic microorganisms or altered self-cells by exclusive pattern recognition molecules (PRMs), such as collectins, ficolins and pentraxins. Recent accumulating evidence shows that the different classes of effector PRMs build up a co-operative network and exert synergistic effects on complement activation. In this review, we describe our updated view of the crosstalk between previously unlinked PRMs in complement activation and the potential pathogenic effects during infection and inflammation.
Collectins ; Complement Activation* ; Complement System Proteins* ; Inflammation

Complement Activation ; Humans ; Thrombosis ; immunology

OBJECTIVETo improve our comprehensions to complement activation by biomaterial and lay the foundation for biosafety evaluation of solid biomaterials together with the corresponding blood contacting medical devices.

METHODSAnalyzed new requirements of current standards on complement activation by solid biomaterial as well as the mechanism of complement activation by solid biomaterial and how to select the related standards for inspection.

RESULTS AND CONCLUSIONThe new edition of international standards has enhanced types of blood contacting medical devices which are appropriate to complement activation test. It is badly in need of establishing the corresponding industry standards to regulate these requirements, since there have no uniform and admissive methods for inspection of complement activation by solid biomaterial.

The capacity of tobacco infusions of Korean cigarettes to activate the complement pathway was investigated in vitro by hemolytic assay. Complement activity was studied using samples of normal rabbit serum incubated at 37 degrees C with tobacco infusions. In all mixtures containing tobacco infusion A, B, C, D, E, F, G, H and I at a concentration of 0.1 : 1, total hemolytic complement showed a progressive decrease of 55.92%, 48.62%, 42.89%, 49.12%, 42.26%, 52.26%, 71.96%, 60.90%, and 61.14% respectively, after 60min of incubation. This study suggests that all tobacco infusions of Korean cigarettes are activators of complement.
Complement Activation* ; Complement Hemolytic Activity Assay ; Complement System Proteins* ; Tobacco Products ; Tobacco*

The polysaccharide B3-PS2 was extracted and purified from Herba Scutellariae Barbatae through chromatography of DEAE-cellulose and Sephacryl S-300 column. Average molecular weight of B3-PS2 was about 1,100 kD. It was composed of Glc, Gal and Ara in the ratio of 2.7:2.7:1.0, along with trace of Man, Rha, Fuc and Xyl. B3-PS2 inhibited complement activation on the classic pathways with CH50 value of (0.23 +/- 0.03) mg mL(-1). The targets of B3-PS2 upon the complement system were C1r, C1s, C3 and C4. These results suggested that anti-complementary activity of B3-PS2 was closed to its positive control heparin. It strongly suggested that the polysaccharide B3-PS2 from Herba Scutellariae Barbatae could be a potential candidate in treating those complement-associated diseases.
Complement Activation ; drug effects ; Complement Inactivating Agents ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; Polysaccharides ; chemistry ; isolation & purification ; pharmacology ; Scutellaria ; chemistry

C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.
Complement Activation ; Complement Pathway, Alternative ; Dichlorodiphenyldichloroethane ; Glomerular Basement Membrane ; Glomerulonephritis ; Glomerulonephritis, Membranoproliferative ; Microscopy, Electron ; Microscopy, Fluorescence ; Pathology ; Prevalence

Henoch-Schonlein purpura (HSP) is a systemic disorder characterized by leukocytoclastic vasculitis that can affect multiple organs predominantly the skin, joints, gastrointestinal tract and kidney. Although the specific pathogenesis of HSP is not known, there are several hypotheses. Although the importance of the complement activation in glomerular injury in HSP has been suggested, the complement levels and the blood pressure in those patients are usually normal and massive proteinuria is not common. And pathologic renal changes also have been reported to show a large variety of glomerular changes. However, to our knowledge, a membranoproliferative glomerulo-nephritis (MPGN) is a rare renal clinicopathologic manifestation of HSP. We report a 6-year-old boy with HSP who developed MPGN with hypertension, massive proteinuria, and hypo-complementemia revealed activation of the classical complement pathway, although we could not exclude the possibility of other hypocomplementemic glomerulonephritis including post-streptococcal acute glomerulonephritis.
Blood Pressure ; Child ; Complement Activation ; Complement Pathway, Classical ; Complement System Proteins ; Gastrointestinal Tract ; Glomerulonephritis ; Glomerulonephritis, Membranoproliferative* ; Humans ; Hypertension ; Joints ; Kidney ; Male ; Proteinuria ; Purpura, Schoenlein-Henoch* ; Skin ; Vasculitis

We experienced a living donor liver transplantation for a 26-month-old girl with complement factor H deficiency. Complement factor H is a plasma protein that regulates the activity of the complement pathway. Complement overactivity induced by complement factor H deficiency is associated with atypical hemolytic uremic syndrome. Liver transplantation can be the proper treatment for this condition. During the liver transplantation of these patients, prevention of the complement overactivation is necessary. Minimizing complement activation, through the use of modalities such as plasma exchange before the surgery and transfusion of fresh frozen plasma throughout the entire perioperative period, may be the key for successful liver transplantation in these patients.
Child, Preschool ; Complement Activation ; Complement Factor H* ; Complement System Proteins ; Female ; Hemolytic-Uremic Syndrome* ; Humans ; Liver Transplantation* ; Living Donors* ; Perioperative Period ; Plasma ; Plasma Exchange

The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.
Animals ; Complement Activation ; genetics ; Complement System Proteins ; deficiency ; genetics ; HLA Antigens ; genetics ; Humans ; Immunity, Innate ; genetics ; Immunologic Deficiency Syndromes ; genetics ; Lectins ; metabolism ; Multigene Family ; Receptors, Complement ; genetics