The contact system in chronic kidney disease and hemodialysis - A cross-sectional study.

Background And Hypothesis: The contact system (CAS) is a part of both the immune system and the coagulation system. The involvement of the CAS in chronic kidney disease (CKD) and hemodialysis (HD) has been documented, yet conflicting findings have hindered a comprehensive understanding. This study aimed to investigate whether CAS activation occurs in patients with chronic kidney failure undergoing HD compared with those undergoing peritoneal dialysis (PD), patients with CKD not receiving replacement therapy, or healthy controls and to assess the impact of HD on CAS from pre- to post-dialysis during a single session of HD.

Plasma Kallikrein Cleaved H-kininogen: An End-Point Marker for Contact Activation and .

Objectives: The contact system consists of coagulation factor XII (FXII), prekallikrein, and H-kininogen (HK) and plays important roles in many diseases. Plasma kallikrein (PKa) cleaved HK (cHK) is a marker of contact activation. Presently, we developed a specific and precise enzyme-linked immunosorbent assay (ELISA) for determination of cHK and

Methods: Cleaved HK specific mouse monoclonal antibodies (mAbs) were generated using a peptide corresponding to the PKa cleavage site on HK as immunogen.

Monitoring process-related impurities in biologics-host cell protein analysis.

During biologics development, manufacturers must demonstrate clearance of host cell impurities and contaminants to ensure drug purity, manufacturing process consistency, and patient safety. Host cell proteins (HCPs) are a major class of process-related impurities and require monitoring and documentation of their presence through development and manufacturing. Even in residual amounts, they are known to affect product quality and efficacy as well as patient safety.

Hemodialysis leads to plasma depletion of lectin complement pathway initiator molecule ficolin-2.

Introduction: This study aimed to investigate changes in complement system-related molecules in patients undergoing hemodialysis.

Methods: Patients >18 years of age on maintenance hemodialysis were included. Using enzyme-linked immunosorbent assays (ELISA) methods complement related molecules ficolin-1, ficolin-2, ficolin-3 mannose-binding lectin, long pentraxin 3, complement activation products C3c, and complement activation potentials were measured before and after a single hemodialysis treatment.

Prediction of survival in amyotrophic lateral sclerosis: a nationwide, Danish cohort study.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials.

Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study.

Background: The complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients.

Methods: This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs).

Local complement activation is associated with primary graft dysfunction after lung transplantation.

BACKGROUNDThe complement system plays a key role in host defense but is activated by ischemia/reperfusion injury (IRI). Primary graft dysfunction (PGD) is a form of acute lung injury occurring predominantly due to IRI, which worsens survival after lung transplantation (LTx). Local complement activation is associated with acute lung injury, but whether it is more reflective of allograft injury compared with systemic activation remains unclear.

Circulating Ficolin-2 and Ficolin-3 Form Heterocomplexes.

The complement system constitutes an important part of the innate immune system. The collectins and the ficolins are soluble pattern recognition molecules that contribute to complement activation via the lectin pathway. During previous experiments with ficolin-2 and ficolin-3, we have observed that the molecules may interact.

A novel approach to evaluate ELISA antibody coverage of host cell proteins-combining ELISA-based immunocapture and mass spectrometry.

Monitoring host cell proteins (HCPs) is one of the most important analytical requirements in production of recombinant biopharmaceuticals to ensure product purity and patient safety. Enzyme-linked immunosorbent assay (ELISA) is the standard method for monitoring HCP clearance. It is important to validate that the critical reagent of an ELISA, the HCP antibody, covers a broad spectrum of the HCPs potentially present in the purified drug substance.

Complement Activation Is Associated With Mortality in Patients With Necrotizing Soft-Tissue Infections-A Prospective Observational Study.

We assessed whether different complement factors and complement activation products were associated with poor outcome in patients with necrotizing soft-tissue infection (NSTI). We conducted a prospective, observational study in an intensive care unit where treatment of NSTI is centralized at a national level. In 135 NSTI patients and 65 control patients, admission levels of MASP-1, MASP-2, MASP-3, C4, C3, complement activation products C4c, C3bc, and terminal complement complex (TCC) were assessed.

Complement related pattern recognition molecules as markers of short-term mortality in intensive care patients.

Objectives: To evaluate the complement related pattern recognition molecules (PRMs) PTX3, MBL, CL-11, ficolin-2 and -3, along with the established marker CRP, to predict 28-day mortality and disease severity of sepsis in patients admitted to the intensive care unit (ICU).

Methods: In a single-center, prospective, observational study 547 patients were included over a period of 18 months. Blood samples were obtained at admission to the ICU and the following 4 days.

Decreased Ficolin-3-mediated Complement Lectin Pathway Activation and Alternative Pathway Amplification During Bacterial Infections in Patients With Type 2 Diabetes Mellitus.

Bacterial infections are frequent and severe in patients with diabetes mellitus. Whether diabetes induces functional alterations in the complement system hampering activation during infection is unknown. We investigated key elements of the complement system during bacterial infections in patients with type 2 diabetes mellitus (T2DM) and compared them to non-diabetic (ND) individuals.

Alpha-cyclodextrin inhibits cholesterol crystal-induced complement-mediated inflammation: A potential new compound for treatment of atherosclerosis.

Background And Aims: Cholesterol crystal (CC)-induced inflammation is a critical step in the development of atherosclerosis. CCs activate the complement system and induce an inflammatory response resulting in phagocytosis of the CCs, production of reactive oxygen species (ROS) and release of cytokines. The cyclodextrin 2-hydroxypropyl-β-cyclodextrin has been found to reduce CC-induced complement activation and induce regression of established atherosclerotic plaques in a mouse model of atherosclerosis, thus inhibition of complement with cyclodextrins is a potential new strategy for treatment of inflammation during atherosclerosis.

Chimeric Proteins Containing MAP-1 and Functional Domains of C4b-Binding Protein Reveal Strong Complement Inhibitory Capacities.

The complement system is a tightly regulated network of proteins involved in defense against pathogens, inflammatory processes, and coordination of the innate and adaptive immune responses. Dysregulation of the complement cascade is associated with many inflammatory disorders. Thus, inhibition of the complement system has emerged as an option for treatment of a range of different inflammatory diseases.

Mannose-binding lectin genotypes and outcome in end-stage renal disease: a prospective cohort study.

Background: Patients with end-stage renal disease (ESRD) have high morbidity and mortality rates, with cardiovascular diseases and infections being the major causes of death. Mannose-binding lectin (MBL) has been suggested to play a protective role in this regard. The aim of this study was to investigate a possible clinical association of MBL genotypes (MBL2) with outcome among patients on dialysis or with a functioning graft.

Prognostic value of lectin pathway molecules and complement proteins in ascitic fluid and blood in patients with liver cirrhosis.

Background And Aim: Patients with liver cirrhosis and ascites have a poor prognosis with increased risk of infection related death, as advanced stages of cirrhosis are associated with immunodeficiency. We aimed to investigate immunologically active molecules in ascitic fluid and blood and their potential association to survival.

Materials And Methods: In an exploratory pilot study; blood and ascitic fluid from 34 patients with liver cirrhosis of different etiology were analyzed for pattern recognition molecules (ficolin-1, ficolin-2, ficolin-3 and MBL) and complement proteins (C4 and C3).

C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques.

Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are serum proteins associated with increased risk of cardiovascular events and these proteins have been shown to interact with the complement system. Whether the pentraxins binds to CC and mediate downstream complement-dependent inflammatory processes remains unknown.

Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine With Morbidity and Mortality in Patients With Necrotizing Soft Tissue Infections.

Background: The nitric oxide system could play an important role in the pathophysiology related to necrotizing soft tissue infection (NSTI). Accordingly, we investigated the association between plasma nitrite level at admission and the presence of septic shock in patients with NSTI. We also evaluated the association between nitrite, asymmetric dimethylarginine (ADMA), L-arginine, L-arginine/ADMA ratio, and outcome.

Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation.

Cholesterol crystals (CC) are abundant in atherosclerotic plaques and promote inflammatory responses via the complement system and inflammasome activation. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (BCD) is a compound that solubilizes lipophilic substances. Recently we have shown that BCD has an anti-inflammatory effect on CC via suppression of the inflammasome and liver X receptor activation.

Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway.

The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex.

Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men.

Insulin resistance is associated with high circulating level of complement factor C3. Animal studies suggest that improper complement activation mediates high-fat-diet-induced insulin resistance. Individuals born with low birth weight (LBW) are at increased risk of developing insulin resistance.

Plasma ficolin levels and risk of nephritis in Danish patients with systemic lupus erythematosus.

Given the scavenging properties of ficolins, we hypothesized that variation in the plasma concentrations of the three ficolins may be associated with development of lupus nephritis (LN), type of LN, end-stage renal disease (ESRD), and/or mortality among patients with systemic lupus erythematosus (SLE). SLE patients attending a Danish tertiary rheumatology referral center were included. Plasma concentrations of ficolin-1, ficolin-2, and ficolin-3 were determined and dichotomized by the median into high and low.

Complementary Roles of the Classical and Lectin Complement Pathways in the Defense against .

infections are associated with a high mortality rate for immunocompromised patients. The complement system is considered to be important in protection against this fungus, yet the course of activation is unclear. The aim of this study was to unravel the role of the classical, lectin, and alternative pathways under both immunocompetent and immunocompromised conditions to provide a relevant dual-perspective on the response against .