Complement System Proteins Research Articles

The role of complement system in thrombotic microangiopathy and its research progress

Thrombotic microangiopathy (TMA) is a group of acute clinical pathological syndromes with common pathological features, which include hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura syndrome. They have many similarities in etiology and clinical presentation. The role of abnormal activation of complement bypass pathway in the genesis and development of HUS has been recognized. More than 100 kinds of complement regulatory factors or gene mutations of complement itself were found to be associated with the development of HUS, which resulted in the decrease of negative complement regulatory protein activity or the increase of complement activation protein function. Abnormal activation of complement system resulted in endothelial injury and thrombosis. Loss of ADAMTS13 activity (<10%) is the most important pathogenesis of TTP. However, there are more and more evidence that complement bypassing pathway is over-regulated and over-activated in the formation of TTP. At present, the research of TMA is focused on finding specific complement-activated biomarkers in patients with various forms of TMA and developing new targeted therapeutic drugs for the disease. Key words: Thrombotic microangiopathies; Complement pathway, alternative; Complement activation; Complement system proteins; Biomarkers

Combining SPR with atomic-force microscopy enables single-molecule insights into activation and suppression of the complement cascade

Activation and suppression of the complement system compete on every serum-exposed surface, host or foreign. Potentially harmful outcomes of this competition depend on surface molecules through mechanisms that remain incompletely understood. Combining surface plasmon resonance (SPR) with atomic force microscopy (AFM), here we studied two complement system proteins at the single-molecule level: C3b, the proteolytically activated form of C3, and factor H (FH), the surface-sensing C3b-binding complement regulator. We used SPR to monitor complement initiation occurring through a positive-feedback loop wherein surface-deposited C3b participates in convertases that cleave C3, thereby depositing more C3b. Over multiple cycles of flowing factor B, factor D, and C3 over the SPR chip, we amplified C3b from ∼20 to ∼220 molecules·μm−2. AFM revealed C3b clusters of up to 20 molecules and solitary C3b molecules deposited up to 200 nm away from the clusters. A force of 0.17 ± 0.02 nanonewtons was needed to pull a single FH molecule, anchored to the AFM probe, from its complex with surface-attached C3b. The extent to which FH molecules stretched before detachment varied widely among complexes. Performing force-distance measurements with FH(D1119G), a variant lacking one of the C3b-binding sites and causing atypical hemolytic uremic syndrome, we found that it detached more uniformly and easily. In further SPR experiments, KD values between FH and C3b on a custom-made chip surface were 5-fold tighter than on commercial chips and similar to those on erythrocytes. These results suggest that the chemistry at the surface on which FH acts drives conformational adjustments that are functionally critical.

Molecular Mechanisms of Complement System Proteins and Matrix Metalloproteinases in the Pathogenesis of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina deteriorates, resulting in the loss of central vision. The key factors associated with the pathogenesis of AMD are age, smoking, dietary, and genetic risk factors. There are few associated and plausible genes involved in AMD pathogenesis. Common genetic variants (with a minor allele frequency of >5% in the population) near the complement genes explain 40-60% of the heritability of AMD. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH, contribute to the formation of drusen and progression of AMD. Similarly, Matrix metalloproteinases (MMPs) that are normally involved in tissue remodeling also play a critical role in the pathogenesis of AMD. MMPs are involved in the degradation of cell debris and lipid deposits beneath retina but with age their functions get affected and result in the drusen formation, succeeding to macular degeneration. In this review, AMD pathology, existing knowledge about the normal and pathological role of complement system proteins and MMPs in the eye is reviewed. The scattered data of complement system proteins, MMPs, drusenogenesis, and lipofusogenesis have been gathered and discussed in detail. This might add new dimensions to the understanding of molecular mechanisms of AMD pathophysiology and might help in finding new therapeutic options for AMD.

Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice

Neurological complications affecting the central nervous system have been reported in adult patients infected by Zika virus (ZIKV) but the underlying mechanisms remain unknown. Here, we report that ZIKV replicates in human and mouse adult brain tissue, targeting mature neurons. ZIKV preferentially targets memory-related brain regions, inhibits hippocampal long-term potentiation and induces memory impairment in adult mice. TNF-α upregulation, microgliosis and upregulation of complement system proteins, C1q and C3, are induced by ZIKV infection. Microglia are found to engulf hippocampal presynaptic terminals during acute infection. Neutralization of TNF-α signaling, blockage of microglial activation or of C1q/C3 prevent synapse and memory impairment in ZIKV-infected mice. Results suggest that ZIKV induces synapse and memory dysfunction via aberrant activation of TNF-α, microglia and complement. Our findings establish a mechanism by which ZIKV affects the adult brain, and point to the need of evaluating cognitive deficits as a potential comorbidity in ZIKV-infected adults.

Time-dependent C5a and C5aR expression in dental pulp cells following stimulation with LTA and LPS.

Clinically, deep decay can lead to inflammation in the dental pulp. Apart from the use of various materials to sooth the inflamed pulp, there is currently no adequate treatment, and the gold standard, calcium hydroxide, that is used to cover the dentin/pulp, has limited effect. Sometimes the pulp will remain infected and cause pulpitis, and ultimately, the pulp will need to be removed. The first principle of oral treatment is to protect the pulp. Therefore, it is necessary to study the immune response and regeneration of pulp cells in conditions of deep decay. Of the terminal complement system proteins, complement 5a (C5a) has the most potent effect compared to complement 3a (C3a) and complement 4a (C4a). C5a is 20- to 2,500-fold stronger than C3a and C4a. The purpose of this study was to elucidate the association between C5a, secreted by complement activation, and the duration of inflammation. Another key goal was to detect the expression of C5a and its receptor, complement 5a receptor (C5aR). To this end, the cells were divided into 4 groups as per stimulation with lipoteichoic acid (LTA) or lipopolysaccharide (LPS) as follows: i) The 1 µg/ml LTA group; ii) the 1 µg/ml LPS group; iii) the 1 µg/ml LTA and 1 µg/ml LPS group; and iv) the PBS-only group, which served as a control. There were 5 time points for all 4 groups: 1, 2, 3, 5 and 7 days. Reverse transcription-quantitative polymerase chain reaction was used to detect the gene expression levels of C5a, C5aR and interleukin (IL)-6 at different time points. Western blot analyses was carried out to detect the expression of C5aR. Transmission electron microscopy was also conducted to assess the ultra-structural features of dental pulp cells. The gene expression trends of C5a and C5aR mRNA were identical. C5a and C5aR mRNA was highly expressed on the second day of LTA or LPS stimulation. However, in the LTA and LPS co-stimulation group, C5a and C5aR mRNA were highly expressed on both the first and second day, with higher levels on the second day. IL-6 expression decreased as time progressed in the LTA only and in the LTA + LPS co-stimulation groups. However, a peak in its expression was observed on the second day in the LPS group. On the whole, this study demonstrates that a 1 µg/ml concentration of LTA and LPS stimulates human dental pulp cells to activate the expression of C5a.

Identification of Potential Novel Interacting Partners for Coagulation Factor XIII B (FXIII-B) Subunit, a Protein Associated with a Rare Bleeding Disorder.

Coagulation factor XIII (FXIII) is a plasma-circulating heterotetrameric pro-transglutaminase complex that is composed of two catalytic FXIII-A and two protective/regulatory FXIII-B subunits. FXIII acts by forming covalent cross-links within a preformed fibrin clots to prevent its premature fibrinolysis. The FXIII-A subunit is known to have pleiotropic roles outside coagulation, but the FXIII-B subunit is a relatively unexplored entity, both structurally as well as functionally. Its discovered roles so far are limited to that of the carrier/regulatory protein of its partner FXIII-A subunit. In the present study, we have explored the co-presence of protein excipients in commercial FXIII plasma concentrate FibrogamminP by combination of protein purification and mass spectrometry-based verification. Complement factor H was one of the co-excipients observed in this analysis. This was followed by performing pull down assays from plasma in order to detect the putative novel interacting partners for the FXIII-B subunit. Complement system proteins, like complement C3 and complement C1q, were amongst the proteins that were pulled down. The only protein that was observed in both experimental set ups was alpha-2-macroglobulin, which might therefore be a putative interacting partner of the FXIII/FXIII-B subunit. Future functional investigations will be needed to understand the physiological significance of this association.

An IgY-based immunoassay to evaluate the biomarker potential of the Tannerella forsythia virulence factor karilysin in human saliva

Tannerella forsythia is a gram-negative anaerobic bacterium that is associated with the development of destructive periodontal disease. T. forsythia secretes the metalloprotease-like enzyme karilysin. Using in vitro systems karilysin has been shown to modulate the host immune response by degradation of complement system proteins and by inactivation of the antimicrobial peptide LL-37 by proteolytic cleavage. This makes karilysin a highly interesting virulence factor to study in the framework of drug development and diagnostics. However, to date the presence of karilysin in clinical samples has not been demonstrated due to the lack of specific probes.In the present work, a high titer and stable affinity-purified avian IgY antibody against karilysin was developed. By surface plasmon resonance imaging the IgY affinity was found to be in the low nanomolar range. The antibody could be used to detect karilysin in saliva samples by immuno-blotting and was specific when tested towards human MMP-3. Furthermore, an avian IgY-based immunoassay was developed, which demonstrated low intra- and interday assay variability (CV's below 10%).Application of the immunoassay on a well-characterized set of saliva samples from adolescents with or without signs of periodontitis showed that it was possible to detect karilysin in saliva. A significant difference in karilysin concentration was found between saliva from participants with signs of periodontitis and saliva from healthy controls (p = .0024). The median of karilysin levels among periodontitis cases was 957 pg/ml (IQR, 499–2132 pg/ml) and the median for controls was 569 pg/ml (IQR, 210–1343 pg/ml).Collectively our data confirm the presence of karilysin in clinical samples. The described IgY-based immunoassay may prove useful as part of protein-based biomarker screenings in the clinic or in point-of care settings.

Changes in the Plasma Protein Composition in Cosmonauts after Space Flight and its Significance for Endothelial Functions

Spaceflight (SF) conditions have a significant impact on the functioning of the human cardiovascular system. The endothelium plays an important role in the process of adaptation to SF factors. Therefore, the detection of biomarkers of endothelial dysfunction is necessary for understanding the molecular mechanisms involved in changes caused by SFs. For this purpose, the blood plasma proteins of 18 Russian cosmonauts were used for quantitative analysis by liquid chromatography with a UPLC 1290 Infinity chromatograph coupled to an Agilent 6490 triple quadrupole mass spectrometer. It was found that a decrease in the circulating plasma volume during the flight followed by the activation of fluid retention at the final stage of flight contributed to the changes in plasma protein concentrations on the first day after landing. We observed a significant increase in the concentration of the S100A9 protein that plays an important role in endothelium functioning and angiogenesis and can serve as a marker of inflammatory reactions. On the first day after landing, the complement system and acute-phase protein concentrations tended to increase, which can adversely affect the functioning of the endothelium.

Immunophysical Evaluation of the Initiating Step in the Formation of the Membrane Attack Complex

The complex between complement system proteins C5b and C6 is the cornerstone for the assembly of the membrane attack complex (MAC, also known as C5b6789n). MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on cell surfaces, as a response of the immune system in fighting pathogens. However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to several complement-mediated autoimmune diseases. We performed a molecular dynamics and electrostatics study to elucidate the mechanism of interaction between C5b and C6 and the formation of the C5b6 complex. The C5b-C6 interface consists of three binding sites stabilized predominantly by van der Waals interactions, and several critical salt bridges and hydrogen bonds. We discuss differences between domains C5d and C3d that lead to mono-functionality of C5d in acting as the scaffold for MAC formation, as opposed to dual functionality of C3d in acting as an opsonin for phagocytosis and as a link between innate and adaptive immunity, based on a comparative sequence, structural, and physicochemical analysis. We also extended our analysis to pathway dynamics to demonstrate the significance of consumption-production rates of C5b, C6 and C5b6 that lead towards MAC formation. Finally, we propose that C5d is a target for drug discovery, aiming to the inhibition of the MAC formation in autoimmune diseases originating from MAC-mediated host cell lysis.

High-throughput proteomic profiling of the fish liver following bacterial infection

BackgroundHigh-throughput proteomics was used to determine the role of the fish liver in defense responses to bacterial infection. This was done using a rainbow trout (Oncorhynchus mykiss) model following infection with Aeromonas salmonicida, the causative agent of furunculosis. The vertebrate liver has multifaceted functions in innate immunity, metabolism, and growth; we hypothesize this tissue serves a dual role in supporting host defense in parallel to metabolic adjustments that promote effective immune function. While past studies have reported mRNA responses to A. salmonicida in salmonids, the impact of bacterial infection on the liver proteome remains uncharacterized in fish.ResultsRainbow trout were injected with A. salmonicida or PBS (control) and liver extracted 48 h later for analysis on a hybrid quadrupole-Orbitrap mass spectrometer. A label-free method was used for protein abundance profiling, which revealed a strong innate immune response along with evidence to support parallel rewiring of metabolic and growth systems. 3076 proteins were initially identified against all proteins (n = 71,293 RefSeq proteins) annotated in a single high-quality rainbow trout reference genome, of which 2433 were maintained for analysis post-quality filtering. Among the 2433 proteins, 109 showed significant differential abundance following A. salmonicida challenge, including many upregulated complement system and acute phase response proteins, in addition to molecules with putative functions that may support metabolic re-adjustments. We also identified novel expansions in the complement system due to gene and whole genome duplication events in salmonid evolutionary history, including eight C3 proteins showing differential changes in abundance.ConclusionsThis study provides the first high-throughput proteomic examination of the fish liver in response to bacterial challenge, revealing novel markers for the host defense response, and evidence of metabolic remodeling in conjunction with activation of innate immunity.

Natural Honey Bee venom Manipulates Human Immune Response

Background: Honey bee venom is an important toxin which has various useful properties. Bee venom possesses various peptides including melittin, apamin, adolapamin and mast cell degranulating peptide. It appears to stimulate cortisone secretion, enhances antibody production, and affects cytokine production. Aim: The aim of the work is to study changes in levels of complement system proteins, C3 and C4, together with C-reactive proteins and rheumatoid factors (CRP and RF) in response to bee venom in subjects exposed naturally to sting with honey bee workers. Subjects and Methods: Subjects (12) were randomly selected from patients visiting El-Mostafa bee house, Elmarg, cairo, Egypt; to get natural bee venom therapy for various diseases. Blood samples (24) were collected from these volunteers, before and after honey bee sting, at the laboratory of Egypt Air Hospital, Cairo, Egypt following the standard protocol. Serum levels of C3 and C4 were measured by radial immunodiffusion technique. CRP was quantitatively measured by in vitro diagnostic test using auto analyzer (Dimension® EXEL) clinical chemistry system. Serum RF was measured by Rapid latex agglutination test for qualitative screening. Result: After exposure of patients to bee sting: all abnormal levels of C3 returned to normal values while abnormal C4 levels did not change; Half of cases that were showing abnormal high CRP levels have dropped to normal levels and All RF positive cases have become negative. Conclusion: The complement system has been activated, in patients, by both classical and alternative pathways before treatment with bee venom where it became only classically activated after treatment. Improved values of both CRP and RF indicate reduction in the inflammatory immune response after exposure of patients to honey bee venom.

Natural Honey Bee venom Manipulates Human Immune Response

Background: Honey bee venom is an important toxin which has various useful properties. Bee venom possesses various peptides including melittin, apamin, adolapamin and mast cell degranulating peptide. It appears to stimulate cortisone secretion, enhances antibody production, and affects cytokine production. Aim: The aim of the work is to study changes in levels of complement system proteins, C3 and C4, together with C-reactive proteins and rheumatoid factors (CRP and RF) in response to bee venom in subjects exposed naturally to sting with honey bee workers. Subjects and Methods: Subjects (12) were randomly selected from patients visiting El-Mostafa bee house, Elmarg, cairo, Egypt; to get natural bee venom therapy for various diseases. Blood samples (24) were collected from these volunteers, before and after honey bee sting, at the laboratory of Egypt Air Hospital, Cairo, Egypt following the standard protocol. Serum levels of C3 and C4 were measured by radial immunodiffusion technique. CRP was quantitatively measured by in vitro diagnostic test using auto analyzer (Dimension® EXEL) clinical chemistry system. Serum RF was measured by Rapid latex agglutination test for qualitative screening. Result: After exposure of patients to bee sting: all abnormal levels of C3 returned to normal values while abnormal C4 levels did not change; Half of cases that were showing abnormal high CRP levels have dropped to normal levels and All RF positive cases have become negative. Conclusion: The complement system has been activated, in patients, by both classical and alternative pathways before treatment with bee venom where it became only classically activated after treatment. Improved values of both CRP and RF indicate reduction in the inflammatory immune response after exposure of patients to honey bee venom.

Proteomic Analysis of Aqueous Humor from Primary Open Angle Glaucoma Patients on Drug Treatment Revealed Altered Complement Activation Cascade.

Primary open angle glaucoma (POAG) is a complex disease and a leading cause of irreversible blindness, and its underlying pathophysiology remains poorly understood. Proteomic characterization of the protein composition of aqueous humor (AH) may identify prognostic candidate proteins involved in pathogenesis and progression of the disease. To delineate the possible mechanisms that lead to POAG, this study adopted state-of-art mass spectrometric technique and analyzed AH of POAG and their respective controls. In total, more than 1000 proteins were identified with false discovery rate of less than 1%. Numerous proteins of complement cascade, immunoglobulin, neuronal and amyloidogenic proteins, which were part of processes like acute-phase and inflammatory response, humoral immune and acute inflammatory response, regulation of complement activation and protein processing were identified. Proteins of complement system underwent significant changes, which correlate to pathogenic events characterizing POAG, including altered complement cascade, astrocyte activation, neural degeneration, and apoptosis. Further, protein modification such as deamidation of complement subcomponent was noted, particularly in POAG. Proteomic analysis of AH allows a better understanding of the mechanism involved in the pathogenesis of POAG.

Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.

Studies in humans have shown a direct association between maternal plasma cholesterol concentrations and infant birthweight. Similarly, previous studies in our laboratory have shown that chow-fed mice lacking apolipoprotein (apo) A-I, the major protein in HDL, have low HDL-cholesterol (HDL-C) concentrations and smaller fetuses in midgestation. In the current study, we measured fetal weights in mice with varying levels of apoA-I gene dose (knockout, wild-type, and transgenic) and examined metabolic pathways known to affect fetal growth. As expected, we found the differences in apoA-I expression led to changes in HDL particle size and protein cargo as well as plasma cholesterol concentrations. Fetal masses correlated directly with maternal plasma cholesterol and apoA-I concentrations, but placental masses and histology did not differ between groups of mice. There was no significant difference in glucose or amino acid transport to the fetus or in expression levels of the glucose (glucose transporter 1 and 2) or amino acid (sodium-coupled neutral amino acid transporter 1 and 2) transporters in whole placentas, although there was a trend for greater uptake of both nutrients in the whole fetal unit (fetus + placenta) of mice with greater apoA-I levels; significant differences in transport rates occurred when mice without apoA-I (knockout) vs. mice with apoA-I (wild-type and transgenic) were compared. Glucose tolerance tests were improved in the mice with the highest level of apoA-I, suggesting increased insulin-induced uptake of glucose by tissues of apoA-I transgenic mice. Thus, maternal HDL is associated with fetal growth, an effect that is likely mediated by plasma cholesterol or other HDL-cargo, including apolipoproteins or complement system proteins. A direct role of enhanced glucose and/or amino acid transport cannot be excluded.-Rebholz, S. L., Melchior, J. T., Davidson, W. S., Jones, H. N., Welge, J. A., Prentice, A. M., Moore, S. E., Woollett, L. A. Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.

Innate and intrinsic immunity in planarians

Planarians in the Phylum Platyhelminthes occupy a peculiar phylogenetic position and have a strong regenerative capacity of their adult tissues, which has aroused general attention. Planarians are spontaneously exposed to various pathogens (microbes and harmful chemicals), but typically survive these challenges. Therefore, these animals can provide useful insights into the evolution of the innate immune system. This review mainly focuses on immune tissues (epidermis, pharynx, and intestine), immune cells (phagocytic reticular cells) and immune genes of planarians. In addition, we provide an overview of the critical proteins in the innate immune system - for example, pattern recognition receptors, complement system proteins, anti-microbial peptides and antioxidant enzymes. In particular, the effectors of the signaling pathways activated upon planarian infection are reviewed.

Heparin Mimetics: Their Therapeutic Potential.

Heparin mimetics are synthetic and semi-synthetic compounds that are highly sulfated, structurally distinct analogues of glycosaminoglycans. These mimetics are often rationally designed to increase potency and binding selectivity towards specific proteins involved in disease manifestations. Some of the major therapeutic arenas towards which heparin mimetics are targeted include: coagulation and thrombosis, cancers, and inflammatory diseases. Although Fondaparinux, a rationally designed heparin mimetic, is now approved for prophylaxis and treatment of venous thromboembolism, the search for novel anticoagulant heparin mimetics with increased affinity and fewer side effects remains a subject of research. However, increasingly, research is focusing on the non-anticoagulant activities of these molecules. Heparin mimetics have potential as anti-cancer agents due to their ability to: (1) inhibit heparanase, an endoglycosidase which facilitates the spread of tumor cells; and (2) inhibit angiogenesis by binding to growth factors. The heparin mimetic, PI-88 is in clinical trials for post-surgical hepatocellular carcinoma and advanced melanoma. The anti-inflammatory properties of heparin mimetics have primarily been attributed to their ability to interact with: complement system proteins, selectins and chemokines; each of which function differently to facilitate inflammation. The efficacy of low/non-anticoagulant heparin mimetics in animal models of different inflammatory diseases has been demonstrated. These findings, plus clinical data that indicates heparin has anti-inflammatory activity, will raise the momentum for developing heparin mimetics as a new class of therapeutic agent for inflammatory diseases.

Hemocompatibility of Ca2+ -Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis.

The present work investigates Ca2+ -crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing-the blood. Hydrogels of wood-derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet-free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.

Complement system and coronary atherosclerosis

Coronary atherosclerosis (CAS) has been recognized as a chronic inflammatory disease in recent years. As an important component of innate immunity, complement system plays an important role in the pathogenesis of CAS. Multiple components of plaque can activate complement proteins, and the activation of complement promotes the progression of plaque lesions in turn. However, recent studies have also found that some proteins of the complement system may also paly an atheroprotective role in the early stage of atherosclerosis. In addition to the direct effects, complement system is also involved in CAS-related pathological changes. Complement proteins may be promising biomarkers, as confirmed by clinical studies which suggest that circulation levels of some complement proteins can predict the risk and prognosis of CAS. This review mainly introduced the origin and activation of complement molecules inside the plaques, their important roles in the pathogenesis of CAS, and the value of complement molecules as potential predictors in clinical.(Chin J Lab Med, 2017, 40: 655-659) Key words: Coronary artery disease; Complement system proteins; Complement activation; Biological markers

Clinical value of detection of complement system related factors in preeclampsia

Gestational hypertension disease is one of the most common complications in pregnancy, and is the second leading cause of maternal mortality in China. In recent years, researchers have found that activation of the complement system plays an important role in the pathogenesis of preeclampsia. In this paper, the authors reviewed previous literature to expound the role of abnormal complement system activation in the pathogenesis of gestational hypertension disease. At the same time, authors will introduce the clinical value of detection of complement system related factors in the diagnosis and differential diagnosis of gestational hypertension disease.(Chin J Lab Med, 2017, 40: 667-671) Key words: Complement system proteins; Complement activation; Hypertension, pregnancy-induced; Pre-eclampsia

Methods and quality control challenges for complement analysis

The complement system is a complex protein network. Complement is important in disease severity and response to therapy. This review summarizes recent advances on the role of complement analysis in complement function or activity, complement factors concentrations, complement activation products, complement autoantibody and genetic analysis. And it also focuses on pre-analytical and post-analytical quality control for complement analysis.(Chin J Lab Med, 2017, 40: 648-651) Key words: Complement system proteins; Complement activation; Autoantibodies; Quality control